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Sample records for epigenetically directed genetic

  1. Genetics and epigenetics of obesity.

    Science.gov (United States)

    Herrera, Blanca M; Keildson, Sarah; Lindgren, Cecilia M

    2011-05-01

    Obesity results from interactions between environmental and genetic factors. Despite a relatively high heritability of common, non-syndromic obesity (40-70%), the search for genetic variants contributing to susceptibility has been a challenging task. Genome wide association (GWA) studies have dramatically changed the pace of detection of common genetic susceptibility variants. To date, more than 40 genetic variants have been associated with obesity and fat distribution. However, since these variants do not fully explain the heritability of obesity, other forms of variation, such as epigenetics marks, must be considered. Epigenetic marks, or "imprinting", affect gene expression without actually changing the DNA sequence. Failures in imprinting are known to cause extreme forms of obesity (e.g. Prader-Willi syndrome), but have also been convincingly associated with susceptibility to obesity. Furthermore, environmental exposures during critical developmental periods can affect the profile of epigenetic marks and result in obesity. We review the most recent evidence for genetic and epigenetic mechanisms involved in the susceptibility and development of obesity. Only a comprehensive understanding of the underlying genetic and epigenetic mechanisms, and the metabolic processes they govern, will allow us to manage, and eventually prevent, obesity. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  2. [Genetics and epigenetics in autism].

    Science.gov (United States)

    Nakayama, Atsuo; Masaki, Shiego; Aoki, Eiko

    2006-11-01

    Autism is a behaviorally defined syndrome characterized by impaired social interaction and communication, and restricted, stereotyped interests and behaviors. Several lines of evidence support the contention that genetic factors are a large component to autism etiology. However, in spite of vigorous genetic studies, no single causative or susceptibility gene common in autism has been identified. Thus multiple susceptibility genes in interaction are considered to account for the disorder. Furthermore, environmental risk factors can accelerate the autism development of. Recent advances in understanding the epigenetic regulation may shed light on the interaction among multiple genetic factors and environmental factors.

  3. Molecular genetics and epigenetics of CACTA elements

    KAUST Repository

    Fedoroff, Nina V.

    2013-08-21

    The CACTA transposons, so named for a highly conserved motif at element ends, comprise one of the most abundant superfamilies of Class 2 (cut-and-paste) plant transposons. CACTA transposons characteristically include subterminal sequences of several hundred nucleotides containing closely spaced direct and inverted repeats of a short, conserved sequence of 14-15 bp. The Supressor-mutator (Spm) transposon, identified and subjected to detailed genetic analysis by Barbara McClintock, remains the paradigmatic element of the CACTA family. The Spm transposon encodes two proteins required for transposition, the transposase (TnpD) and a regulatory protein (TnpA) that binds to the subterminal repeats. Spm expression is subject to both genetic and epigenetic regulation. The Spm-encoded TnpA serves as an activator of the epigenetically inactivated, methylated Spm, stimulating both transient and heritable activation of the transposon. TnpA also serves as a negative regulator of the demethylated active element promoter and is required, in addition to the TnpD, for transposition. © Springer Science+Business Media, New York 2013.

  4. Genetics and epigenetics of eating disorders

    Directory of Open Access Journals (Sweden)

    Yilmaz Z

    2015-03-01

    Full Text Available Zeynep Yilmaz,1 J Andrew Hardaway,1 Cynthia M Bulik1–3 1Department of Psychiatry, 2Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 3Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden Abstract: Eating disorders (EDs are serious psychiatric conditions influenced by biological, psychological, and sociocultural factors. A better understanding of the genetics of these complex traits and the development of more sophisticated molecular biology tools have advanced our understanding of the etiology of EDs. The aim of this review is to critically evaluate the literature on the genetic research conducted on three major EDs: anorexia nervosa, bulimia nervosa, and binge eating disorder. We will first review the diagnostic criteria, clinical features, prevalence, and prognosis of anorexia nervosa, bulimia nervosa, and binge eating disorder, followed by a review of family, twin, and adoption studies. We then review the history of genetic studies of EDs covering linkage analysis, candidate-gene association studies, genome-wide association studies, and the study of rare variants in EDs. Our review also incorporates a translational perspective by covering animal models of ED-related phenotypes. Finally, we review the nascent field of epigenetics of EDs and a look forward to future directions for ED genetic research. Keywords: anorexia nervosa, binge eating disorder, bulimia nervosa, animal models, genome-wide association studies, high-throughput sequencing

  5. Genetic alterations and epigenetic changes in hepatocarcinogenesis

    Directory of Open Access Journals (Sweden)

    Luz Stella Hoyos Giraldo

    2007-02-01

    Full Text Available

    Hepatocarcinogenesis as hepatocellular carcinoma (HCC is associated with background of chronic liver disease usually in association with cirrhosis, marked hepatic fibrosis, hepatitis B virus (HBV and/or hepatitis virus (HCV infection, chronic inflammation, Aflatoxin B1(AFB1 exposure, chronic alcoholism, metabolic disorder of the liver and necroinflamatory liver disease. Hepatocarcinogenesis involve two mechanisms, genetic alterations (with changes in the cell's DNA sequence and epigenetic changes (without changes in the cell's DNA sequence, but changes in the pattern of gene expression that can persist through one or more generations (somatic sense. Hepatocarcinogenesis is associated with activation of oncogenes and decreased expression of tumor suppressor genes (TSG; include those involved in cell cycle control, apoptosis, DNA repair, immortalization and angiogenesis. AFB1 is metabolized in the liver into a potent carcinogen, aflatoxin 8, 9-epoxide, which is detoxified by epoxide hydrolase (EPHX and glutathione S-transferase M1 (GSTM1.

    A failure of detoxification processes can allow to mutagenic metabolite to bind to DNA and inducing P53 mutation. Genetic polymorphism of EPHX and GSTM1 can make individuals more susceptible to AFB1. Epigenetic inactivation of GSTP1 by promoter hypermethylation plays a role in the development of HCC because, it leads that electrophilic metabolite increase DNA damage and mutations. HBV DNA integration into the host chromosomal DNA of hepatocytes has been detected in HBV-related HCC.

    DNA tumor viruses cause cancer mainly by interfering with cell cycle controls, and activating the cell's replication machinery by blocking the action of key TSG. HBx protein is a

  6. Genetics and epigenetics of obesity

    OpenAIRE

    Herrera, Blanca M.; Keildson, Sarah; Lindgren, Cecilia M.

    2011-01-01

    Obesity results from interactions between environmental and genetic factors. Despite a relatively high heritability of common, non-syndromic obesity (40?70%), the search for genetic variants contributing to susceptibility has been a challenging task. Genome wide association (GWA) studies have dramatically changed the pace of detection of common genetic susceptibility variants. To date, more than 40 genetic variants have been associated with obesity and fat distribution. However, since these v...

  7. Genetics and epigenetics of rheumatoid arthritis

    Science.gov (United States)

    Viatte, Sebastien; Plant, Darren; Raychaudhuri, Soumya

    2013-01-01

    Investigators have made key advances in rheumatoid arthritis (RA) genetics in the past 10 years. Although genetic studies have had limited influence on clinical practice and drug discovery, they are currently generating testable hypotheses to explain disease pathogenesis. Firstly, we review here the major advances in identifying RA genetic susceptibility markers both within and outside of the MHC. Understanding how genetic variants translate into pathogenic mechanisms and ultimately into phenotypes remains a mystery for most of the polymorphisms that confer susceptibility to RA, but functional data are emerging. Interplay between environmental and genetic factors is poorly understood and in need of further investigation. Secondly, we review current knowledge of the role of epigenetics in RA susceptibility. Differences in the epigenome could represent one of the ways in which environmental exposures translate into phenotypic outcomes. The best understood epigenetic phenomena include post-translational histone modifications and DNA methylation events, both of which have critical roles in gene regulation. Epigenetic studies in RA represent a new area of research with the potential to answer unsolved questions. PMID:23381558

  8. Genetic and epigenetic risks of assisted reproduction.

    Science.gov (United States)

    Jiang, Ziru; Wang, Yinyu; Lin, Jing; Xu, Jingjing; Ding, Guolian; Huang, Hefeng

    2017-10-01

    Assisted reproductive technology (ART) is used primarily for infertility treatments to achieve pregnancy and involves procedures such as in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), and cryopreservation. Moreover, preimplantation genetic diagnosis (PGD) of ART is used in couples for genetic reasons. In ART treatments, gametes and zygotes are exposed to a series of non-physiological processes and culture media. Although the majority of children born with this treatment are healthy, some concerns remain regarding the safety of this technology. Animal studies and follow-up studies of ART-borne children suggested that ART was associated with an increased incidence of genetic, physical, or developmental abnormalities, although there are also observations that contradict these findings. As IVF, ICSI, frozen-thawed embryo transfer, and PGD manipulate gametes and embryo at a time that is important for reprogramming, they may affect epigenetic stability, leading to gamete/embryo origins of adult diseases. In fact, ART offspring have been reported to have an increased risk of gamete/embryo origins of adult diseases, such as early-onset diabetes, cardiovascular disease, and so on. In this review, we will discuss evidence related to genetic, especially epigenetic, risks of assisted reproduction. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Obesity and diabetes: from genetics to epigenetics.

    Science.gov (United States)

    Burgio, Ernesto; Lopomo, Angela; Migliore, Lucia

    2015-04-01

    Obesity is becoming an epidemic health problem. During the last years not only genetic but also, and primarily, environmental factors have been supposed to contribute to the susceptibility to weight gain or to develop complications such as type 2 diabetes. In spite of the intense efforts to identify genetic predisposing variants, progress has been slow and success limited, and the common obesity susceptibility variants identified only explains a small part of the individual variation in risk. Moreover, there is evidence that the current epidemic of obesity and diabetes is environment-driven. Recent studies indicate that normal metabolic regulation during adulthood besides requiring a good balance between energy intake and energy expenditure, can be also affected by pre- and post-natal environments. In fact, maternal nutritional constraint during pregnancy can alter the metabolic phenotype of the offspring by means of epigenetic regulation of specific genes, and this can be passed to the next generations. Studies focused on epigenetic marks in obesity found altered methylation and/or histone acetylation levels in genes involved in specific but also in more general metabolic processes. Recent researches point out the continuous increase of "obesogens", in the environment and food chains, above all endocrine disruptors, chemicals that interfere with many homeostatic mechanisms. Taken into account the already existing data on the effects of obesogens, and the multiple potential targets with which they might interfere daily, it seems likely that the exposure to obesogens can have an important role in the obesity and diabesity pandemic.

  10. Small RNA-directed epigenetic natural variation in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Jixian Zhai

    2008-04-01

    Full Text Available Progress in epigenetics has revealed mechanisms that can heritably regulate gene function independent of genetic alterations. Nevertheless, little is known about the role of epigenetics in evolution. This is due in part to scant data on epigenetic variation among natural populations. In plants, small interfering RNA (siRNA is involved in both the initiation and maintenance of gene silencing by directing DNA methylation and/or histone methylation. Here, we report that, in the model plant Arabidopsis thaliana, a cluster of approximately 24 nt siRNAs found at high levels in the ecotype Landsberg erecta (Ler could direct DNA methylation and heterochromatinization at a hAT element adjacent to the promoter of FLOWERING LOCUS C (FLC, a major repressor of flowering, whereas the same hAT element in ecotype Columbia (Col with almost identical DNA sequence, generates a set of low abundance siRNAs that do not direct these activities. We have called this hAT element MPF for Methylated region near Promoter of FLC, although de novo methylation triggered by an inverted repeat transgene at this region in Col does not alter its FLC expression. DNA methylation of the Ler allele MPF is dependent on genes in known silencing pathways, and such methylation is transmissible to Col by genetic crosses, although with varying degrees of penetrance. A genome-wide comparison of Ler and Col small RNAs identified at least 68 loci matched by a significant level of approximately 24 nt siRNAs present specifically in Ler but not Col, where nearly half of the loci are related to repeat or TE sequences. Methylation analysis revealed that 88% of the examined loci (37 out of 42 were specifically methylated in Ler but not Col, suggesting that small RNA can direct epigenetic differences between two closely related Arabidopsis ecotypes.

  11. Genetics and epigenetics of autism: A Review.

    Science.gov (United States)

    Waye, Mary M Y; Cheng, Ho Yu

    2018-04-01

    Autism is a developmental disorder that starts before age 3 years, and children with autism have impairment in both social interaction and communication, and have restricted, repetitive, and stereotyped patterns of behavior, interests, and activities. There is a strong heritable component of autism and autism spectrum disorder (ASD) as studies have shown that parents who have a child with ASD have a 2-18% chance of having a second child with ASD. The prevalence of autism and ASD have been increasing during the last 3 decades and much research has been carried out to understand the etiology, so as to develop novel preventive and treatment strategies. This review aims at summarizing the latest research studies related to autism and ASD, focusing not only on the genetics but also some epigenetic findings of autism/ASD. Some promising areas of research using transgenic/knockout animals and some ideas related to potential novel treatment and prevention strategies will be discussed. © 2017 The Chinese University of Hong Kong. Psychiatry and Clinical Neurosciences © 2017 Japanese Society of Psychiatry and Neurology.

  12. Genetic and epigenetic variations induced by wheat-rye 2R and 5R monosomic addition lines.

    Science.gov (United States)

    Fu, Shulan; Sun, Chuanfei; Yang, Manyu; Fei, Yunyan; Tan, Feiqun; Yan, Benju; Ren, Zhenglong; Tang, Zongxiang

    2013-01-01

    Monosomic alien addition lines (MAALs) can easily induce structural variation of chromosomes and have been used in crop breeding; however, it is unclear whether MAALs will induce drastic genetic and epigenetic alterations. In the present study, wheat-rye 2R and 5R MAALs together with their selfed progeny and parental common wheat were investigated through amplified fragment length polymorphism (AFLP) and methylation-sensitive amplification polymorphism (MSAP) analyses. The MAALs in different generations displayed different genetic variations. Some progeny that only contained 42 wheat chromosomes showed great genetic/epigenetic alterations. Cryptic rye chromatin has introgressed into the wheat genome. However, one of the progeny that contained cryptic rye chromatin did not display outstanding genetic/epigenetic variation. 78 and 49 sequences were cloned from changed AFLP and MSAP bands, respectively. Blastn search indicated that almost half of them showed no significant similarity to known sequences. Retrotransposons were mainly involved in genetic and epigenetic variations. Genetic variations basically affected Gypsy-like retrotransposons, whereas epigenetic alterations affected Copia-like and Gypsy-like retrotransposons equally. Genetic and epigenetic variations seldom affected low-copy coding DNA sequences. The results in the present study provided direct evidence to illustrate that monosomic wheat-rye addition lines could induce different and drastic genetic/epigenetic variations and these variations might not be caused by introgression of rye chromatins into wheat. Therefore, MAALs may be directly used as an effective means to broaden the genetic diversity of common wheat.

  13. Genetic, epigenetic and exogenetic information in development and evolution.

    Science.gov (United States)

    Griffiths, Paul E

    2017-10-06

    The idea that development is the expression of information accumulated during evolution and that heredity is the transmission of this information is surprisingly hard to cash out in strict, scientific terms. This paper seeks to do so using the sense of information introduced by Francis Crick in his sequence hypothesis and central dogma of molecular biology. It focuses on Crick's idea of precise determination. This is analysed using an information-theoretic measure of causal specificity. This allows us to reconstruct some of Crick's claims about information in transcription and translation. Crick's approach to information has natural extensions to non-coding regions of DNA, to epigenetic marks, and to the genetic or environmental upstream causes of those epigenetic marks. Epigenetic information cannot be reduced to genetic information. The existence of biological information in epigenetic and exogenetic factors is relevant to evolution as well as to development.

  14. The role of epigenetics in genetic and environmental epidemiology.

    Science.gov (United States)

    Ladd-Acosta, Christine; Fallin, M Daniele

    2016-02-01

    Epidemiology is the branch of science that investigates the causes and distribution of disease in populations in order to provide preventative measures and promote human health. The fields of genetic and environmental epidemiology primarily seek to identify genetic and environmental risk factors for disease, respectively. Epigenetics is emerging as an important piece of molecular data to include in these studies because it can provide mechanistic insights into genetic and environmental risk factors for disease, identify potential intervention targets, provide biomarkers of exposure, illuminate gene-environment interactions and help localize disease-relevant genomic regions. Here, we describe the importance of including epigenetics in genetic and environmental epidemiology studies, provide a conceptual framework when considering epigenetic data in population-based studies and touch upon the many challenges that lie ahead.

  15. Genetic and epigenetic control of plant heat responses

    Directory of Open Access Journals (Sweden)

    Junzhong eLiu

    2015-04-01

    Full Text Available Plants have evolved sophisticated genetic and epigenetic regulatory systems to respond quickly to unfavorable environmental conditions such as heat, cold, drought, and pathogen infections. In particular, heat greatly affects plant growth and development, immunity and circadian rhythm, and poses a serious threat to the global food supply. According to temperatures exposing, heat can be usually classified as warm ambient temperature (about 22-27℃, high temperature (27-30℃ and extremely high temperature (37-42℃, also known as heat stress for the model plant Arabidopsis thaliana. The genetic mechanisms of plant responses to heat have been well studied, mainly focusing on elevated ambient temperature-mediated morphological acclimation and acceleration of flowering, modulation of plant immunity and circadian clock by high temperatures, and thermotolerance to heat stress. Recently, great progress has been achieved on epigenetic regulation of heat responses, including DNA methylation, histone modifications, histone variants, ATP-dependent chromatin remodeling, histone chaperones, small RNAs, long non-coding RNAs and other undefined epigenetic mechanisms. These epigenetic modifications regulate the expression of heat-responsive genes and function to prevent heat-related damage. This review focuses on recent progresses regarding the genetic and epigenetic control of heat responses in plants, and pays more attention to the role of the major epigenetic mechanisms in plant heat responses. Further research perspectives are also discussed.

  16. Early Determinants of Obesity: Genetic, Epigenetic, and In Utero Influences

    Directory of Open Access Journals (Sweden)

    Kyung E. Rhee

    2012-01-01

    Full Text Available There is an emerging body of work indicating that genes, epigenetics, and the in utero environment can impact whether or not a child is obese. While certain genes have been identified that increase one’s risk for becoming obese, other factors such as excess gestational weight gain, gestational diabetes mellitus, and smoking can also influence this risk. Understanding these influences can help to inform which behaviors and exposures should be targeted if we are to decrease the prevalence of obesity. By helping parents and young children change certain behaviors and exposures during critical time periods, we may be able to alter or modify one’s genetic predisposition. However, further research is needed to determine which efforts are effective at decreasing the incidence of obesity and to develop new methods of prevention. In this paper, we will discuss how genes, epigenetics, and in utero influences affect the development of obesity. We will then discuss current efforts to alter these influences and suggest future directions for this work.

  17. The role of non-genetic inheritance in evolutionary rescue: epigenetic buffering, heritable bet hedging and epigenetic traps.

    Science.gov (United States)

    O'Dea, Rose E; Noble, Daniel W A; Johnson, Sheri L; Hesselson, Daniel; Nakagawa, Shinichi

    2016-01-01

    Rapid environmental change is predicted to compromise population survival, and the resulting strong selective pressure can erode genetic variation, making evolutionary rescue unlikely. Non-genetic inheritance may provide a solution to this problem and help explain the current lack of fit between purely genetic evolutionary models and empirical data. We hypothesize that epigenetic modifications can facilitate evolutionary rescue through 'epigenetic buffering'. By facilitating the inheritance of novel phenotypic variants that are generated by environmental change-a strategy we call 'heritable bet hedging'-epigenetic modifications could maintain and increase the evolutionary potential of a population. This process may facilitate genetic adaptation by preserving existing genetic variation, releasing cryptic genetic variation and/or facilitating mutations in functional loci. Although we show that examples of non-genetic inheritance are often maladaptive in the short term, accounting for phenotypic variance and non-adaptive plasticity may reveal important evolutionary implications over longer time scales. We also discuss the possibility that maladaptive epigenetic responses may be due to 'epigenetic traps', whereby evolutionarily novel factors (e.g. endocrine disruptors) hack into the existing epigenetic machinery. We stress that more ecologically relevant work on transgenerational epigenetic inheritance is required. Researchers conducting studies on transgenerational environmental effects should report measures of phenotypic variance, so that the possibility of both bet hedging and heritable bet hedging can be assessed. Future empirical and theoretical work is required to assess the relative importance of genetic and epigenetic variation, and their interaction, for evolutionary rescue.

  18. From Genetics to Epigenetics: New Perspectives in Tourette Syndrome Research

    Science.gov (United States)

    Pagliaroli, Luca; Vető, Borbála; Arányi, Tamás; Barta, Csaba

    2016-01-01

    Gilles de la Tourette Syndrome (TS) is a neurodevelopmental disorder marked by the appearance of multiple involuntary motor and vocal tics. TS presents high comorbidity rates with other disorders such as attention deficit hyperactivity disorder (ADHD) and obsessive compulsive disorder (OCD). TS is highly heritable and has a complex polygenic background. However, environmental factors also play a role in the manifestation of symptoms. Different epigenetic mechanisms may represent the link between these two causalities. Epigenetic regulation has been shown to have an impact in the development of many neuropsychiatric disorders, however very little is known about its effects on Tourette Syndrome. This review provides a summary of the recent findings in genetic background of TS, followed by an overview on different epigenetic mechanisms, such as DNA methylation, histone modifications, and non-coding RNAs in the regulation of gene expression. Epigenetic studies in other neurological and psychiatric disorders are discussed along with the TS-related epigenetic findings available in the literature to date. Moreover, we are proposing that some general epigenetic mechanisms seen in other neuropsychiatric disorders may also play a role in the pathogenesis of TS. PMID:27462201

  19. Ayurveda: Science of life, genetics, and epigenetics.

    Science.gov (United States)

    Sharma, Hari

    2016-01-01

    Ayurveda is a traditional system of medicine originated in the ancient Vedic times of India. This body of knowledge is found in well-documented texts such as the Charaka Samhita and Sushruta Samhita , and describes physiology and interrelated systems of the body, variations in human constitution, surgery, herbal use, and health-promoting recommendations. Ayurveda is translated as the "Science of Life;" Ayus = Life, and Veda = knowledge/science. The principles and treatment modalities have endured over time. For Ayurveda to be appreciated by Western medical researchers, this traditional system of medicine needs to be understood in terms of modern science. The current theories of physiology that support Ayurvedic approaches need to be explored. Herein, one approach of how the realm of epigenetics can help elucidate the mechanisms of Ayurveda has been described.

  20. Epigenetics of the yeast galactose genetic switch

    Indian Academy of Sciences (India)

    Prakash

    wiped out if the genetic program is not equipped to adapt to ... In this article we review some of the recent attempts made to understand the importance ..... Induction kinetics of GAL gene expression in these two cultures was determined.

  1. Mouse-human experimental epigenetic analysis unmasks dietary targets and genetic liability for diabetic phenotypes

    Science.gov (United States)

    Multhaup, Michael L.; Seldin, Marcus; Jaffe, Andrew E.; Lei, Xia; Kirchner, Henriette; Mondal, Prosenjit; Li, Yuanyuan; Rodriguez, Varenka; Drong, Alexander; Hussain, Mehboob; Lindgren, Cecilia; McCarthy, Mark; Näslund, Erik; Zierath, Juleen R.; Wong, G. William; Feinberg, Andrew P.

    2015-01-01

    SUMMARY Using a functional approach to investigate the epigenetics of Type 2 Diabetes (T2D), we combine three lines of evidence – diet-induced epigenetic dysregulation in mouse, epigenetic conservation in humans, and T2D clinical risk evidence – to identify genes implicated in T2D pathogenesis through epigenetic mechanisms related to obesity. Beginning with dietary manipulation of genetically homogeneous mice, we identify differentially DNA-methylated genomic regions. We then replicate these results in adipose samples from lean and obese patients pre- and post-Roux-en-Y gastric bypass, identifying regions where both the location and direction of methylation change is conserved. These regions overlap with 27 genetic T2D risk loci, only one of which was deemed significant by GWAS alone. Functional analysis of genes associated with these regions revealed four genes with roles in insulin resistance, demonstrating the potential general utility of this approach for complementing conventional human genetic studies by integrating cross-species epigenomics and clinical genetic risk. PMID:25565211

  2. Genetic and epigenetic variations induced by wheat-rye 2R and 5R monosomic addition lines.

    Directory of Open Access Journals (Sweden)

    Shulan Fu

    Full Text Available BACKGROUND: Monosomic alien addition lines (MAALs can easily induce structural variation of chromosomes and have been used in crop breeding; however, it is unclear whether MAALs will induce drastic genetic and epigenetic alterations. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, wheat-rye 2R and 5R MAALs together with their selfed progeny and parental common wheat were investigated through amplified fragment length polymorphism (AFLP and methylation-sensitive amplification polymorphism (MSAP analyses. The MAALs in different generations displayed different genetic variations. Some progeny that only contained 42 wheat chromosomes showed great genetic/epigenetic alterations. Cryptic rye chromatin has introgressed into the wheat genome. However, one of the progeny that contained cryptic rye chromatin did not display outstanding genetic/epigenetic variation. 78 and 49 sequences were cloned from changed AFLP and MSAP bands, respectively. Blastn search indicated that almost half of them showed no significant similarity to known sequences. Retrotransposons were mainly involved in genetic and epigenetic variations. Genetic variations basically affected Gypsy-like retrotransposons, whereas epigenetic alterations affected Copia-like and Gypsy-like retrotransposons equally. Genetic and epigenetic variations seldom affected low-copy coding DNA sequences. CONCLUSIONS/SIGNIFICANCE: The results in the present study provided direct evidence to illustrate that monosomic wheat-rye addition lines could induce different and drastic genetic/epigenetic variations and these variations might not be caused by introgression of rye chromatins into wheat. Therefore, MAALs may be directly used as an effective means to broaden the genetic diversity of common wheat.

  3. Stem Cell Technology for (Epi)genetic Brain Disorders.

    Science.gov (United States)

    Riemens, Renzo J M; Soares, Edilene S; Esteller, Manel; Delgado-Morales, Raul

    2017-01-01

    Despite the enormous efforts of the scientific community over the years, effective therapeutics for many (epi)genetic brain disorders remain unidentified. The common and persistent failures to translate preclinical findings into clinical success are partially attributed to the limited efficiency of current disease models. Although animal and cellular models have substantially improved our knowledge of the pathological processes involved in these disorders, human brain research has generally been hampered by a lack of satisfactory humanized model systems. This, together with our incomplete knowledge of the multifactorial causes in the majority of these disorders, as well as a thorough understanding of associated (epi)genetic alterations, has been impeding progress in gaining more mechanistic insights from translational studies. Over the last years, however, stem cell technology has been offering an alternative approach to study and treat human brain disorders. Owing to this technology, we are now able to obtain a theoretically inexhaustible source of human neural cells and precursors in vitro that offer a platform for disease modeling and the establishment of therapeutic interventions. In addition to the potential to increase our general understanding of how (epi)genetic alterations contribute to the pathology of brain disorders, stem cells and derivatives allow for high-throughput drugs and toxicity testing, and provide a cell source for transplant therapies in regenerative medicine. In the current chapter, we will demonstrate the validity of human stem cell-based models and address the utility of other stem cell-based applications for several human brain disorders with multifactorial and (epi)genetic bases, including Parkinson's disease (PD), Alzheimer's disease (AD), fragile X syndrome (FXS), Angelman syndrome (AS), Prader-Willi syndrome (PWS), and Rett syndrome (RTT).

  4. From Mendel to epigenetics: History of genetics.

    Science.gov (United States)

    Gayon, Jean

    2016-01-01

    The origins of genetics are to be found in Gregor Mendel's memoir on plant hybridization (1865). However, the word 'genetics' was only coined in 1906, to designate the new science of heredity. Founded upon the Mendelian method for analyzing the products of crosses, this science is distinguished by its explicit purpose of being a general 'science of heredity', and by the introduction of totally new biological concepts (in particular those of gene, genotype, and phenotype). In the 1910s, Mendelian genetics fused with the chromosomal theory of inheritance, giving rise to what is still called 'classical genetics'. Within this framework, the gene is simultaneously a unit of function and transmission, a unit of recombination, and of mutation. Until the early 1950s, these concepts of the gene coincided. But when DNA was found to be the material basis of inheritance, this congruence dissolved. Then began the venture of molecular biology, which has never stopped revealing the complexity of the way in which hereditary material functions. Copyright © 2016 Académie des sciences. Published by Elsevier SAS. All rights reserved.

  5. Genetic and epigenetic alterations induced by different levels of rye genome integration in wheat recipient.

    Science.gov (United States)

    Zheng, X L; Zhou, J P; Zang, L L; Tang, A T; Liu, D Q; Deng, K J; Zhang, Y

    2016-06-17

    The narrow genetic variation present in common wheat (Triticum aestivum) varieties has greatly restricted the improvement of crop yield in modern breeding systems. Alien addition lines have proven to be an effective means to broaden the genetic diversity of common wheat. Wheat-rye addition lines, which are the direct bridge materials for wheat improvement, have been wildly used to produce new wheat cultivars carrying alien rye germplasm. In this study, we investigated the genetic and epigenetic alterations in two sets of wheat-rye disomic addition lines (1R-7R) and the corresponding triticales. We used expressed sequence tag-simple sequence repeat, amplified fragment length polymorphism, and methylation-sensitive amplification polymorphism analyses to analyze the effects of the introduction of alien chromosomes (either the entire genome or sub-genome) to wheat genetic background. We found obvious and diversiform variations in the genomic primary structure, as well as alterations in the extent and pattern of the genomic DNA methylation of the recipient. Meanwhile, these results also showed that introduction of different rye chromosomes could induce different genetic and epigenetic alterations in its recipient, and the genetic background of the parents is an important factor for genomic and epigenetic variation induced by alien chromosome addition.

  6. Genetic & epigenetic approach to human obesity

    Directory of Open Access Journals (Sweden)

    K Rajender Rao

    2014-01-01

    Full Text Available Obesity is an important clinical and public health challenge, epitomized by excess adipose tissue accumulation resulting from an imbalance in energy intake and energy expenditure. It is a forerunner for a variety of other diseases such as type-2-diabetes (T2D, cardiovascular diseases, some types of cancer, stroke, hyperlipidaemia and can be fatal leading to premature death. Obesity is highly heritable and arises from the interplay of multiple genes and environmental factors. Recent advancements in Genome-wide association studies (GWAS have shown important steps towards identifying genetic risks and identification of genetic markers for lifestyle diseases, especially for a metabolic disorder like obesity. According to the 12 th u0 pdate of Human Obesity Gene Map there are 253 quantity trait loci (QTL for obesity related phenotypes from 61 genome wide scan studies. Contribution of genetic propensity of individual ethnic and racial variations in obesity is an active area of research. Further, understanding its complexity as to how these variations could influence ones susceptibility to become or remain obese will lead us to a greater understanding of how obesity occurs and hopefully, how to prevent and treat this condition. In this review, various strategies adapted for such an analysis based on the recent advances in genome wide and functional variations in human obesity are discussed.

  7. EpiGeNet: A Graph Database of Interdependencies Between Genetic and Epigenetic Events in Colorectal Cancer.

    Science.gov (United States)

    Balaur, Irina; Saqi, Mansoor; Barat, Ana; Lysenko, Artem; Mazein, Alexander; Rawlings, Christopher J; Ruskin, Heather J; Auffray, Charles

    2017-10-01

    The development of colorectal cancer (CRC)-the third most common cancer type-has been associated with deregulations of cellular mechanisms stimulated by both genetic and epigenetic events. StatEpigen is a manually curated and annotated database, containing information on interdependencies between genetic and epigenetic signals, and specialized currently for CRC research. Although StatEpigen provides a well-developed graphical user interface for information retrieval, advanced queries involving associations between multiple concepts can benefit from more detailed graph representation of the integrated data. This can be achieved by using a graph database (NoSQL) approach. Data were extracted from StatEpigen and imported to our newly developed EpiGeNet, a graph database for storage and querying of conditional relationships between molecular (genetic and epigenetic) events observed at different stages of colorectal oncogenesis. We illustrate the enhanced capability of EpiGeNet for exploration of different queries related to colorectal tumor progression; specifically, we demonstrate the query process for (i) stage-specific molecular events, (ii) most frequently observed genetic and epigenetic interdependencies in colon adenoma, and (iii) paths connecting key genes reported in CRC and associated events. The EpiGeNet framework offers improved capability for management and visualization of data on molecular events specific to CRC initiation and progression.

  8. Asymmetric strand segregation: epigenetic costs of genetic fidelity?

    Directory of Open Access Journals (Sweden)

    Diane P Genereux

    2009-06-01

    Full Text Available Asymmetric strand segregation has been proposed as a mechanism to minimize effective mutation rates in epithelial tissues. Under asymmetric strand segregation, the double-stranded molecule that contains the oldest DNA strand is preferentially targeted to the somatic stem cell after each round of DNA replication. This oldest DNA strand is expected to have fewer errors than younger strands because some of the errors that arise on daughter strands during their synthesis fail to be repaired. Empirical findings suggest the possibility of asymmetric strand segregation in a subset of mammalian cell lineages, indicating that it may indeed function to increase genetic fidelity. However, the implications of asymmetric strand segregation for the fidelity of epigenetic information remain unexplored. Here, I explore the impact of strand-segregation dynamics on epigenetic fidelity using a mathematical-modelling approach that draws on the known molecular mechanisms of DNA methylation and existing rate estimates from empirical methylation data. I find that, for a wide range of starting methylation densities, asymmetric -- but not symmetric -- strand segregation leads to systematic increases in methylation levels if parent strands are subject to de novo methylation events. I found that epigenetic fidelity can be compromised when enhanced genetic fidelity is achieved through asymmetric strand segregation. Strand segregation dynamics could thus explain the increased DNA methylation densities that are observed in structured cellular populations during aging and in disease.

  9. Epigenetics and cerebral organoids: promising directions in autism spectrum disorders.

    Science.gov (United States)

    Forsberg, Sheena Louise; Ilieva, Mirolyuba; Maria Michel, Tanja

    2018-01-10

    Autism spectrum disorders (ASD) affect 1 in 68 children in the US according to the Centers for Disease Control and Prevention (CDC). It is characterized by impairments in social interactions and communication, restrictive and repetitive patterns of behaviors, and interests. Owing to disease complexity, only a limited number of treatment options are available mainly for children that alleviate but do not cure the debilitating symptoms. Studies confirm a genetic link, but environmental factors, such as medications, toxins, and maternal infection during pregnancy, as well as birth complications also play a role. Some studies indicate a set of candidate genes with different DNA methylation profiles in ASD compared to healthy individuals. Thus epigenetic alterations could help bridging the gene-environment gap in deciphering the underlying neurobiology of autism. However, epigenome-wide association studies (EWAS) have mainly included a very limited number of postmortem brain samples. Hence, cellular models mimicking brain development in vitro will be of great importance to study the critical epigenetic alterations and when they might happen. This review will give an overview of the state of the art concerning knowledge on epigenetic changes in autism and how new, cutting edge expertise based on three-dimensional (3D) stem cell technology models (brain organoids) can contribute in elucidating the multiple aspects of disease mechanisms.

  10. A symbiotic liaison between the genetic and epigenetic code

    Directory of Open Access Journals (Sweden)

    Holger eHeyn

    2014-05-01

    Full Text Available With rapid advances in sequencing technologies, we are undergoing a paradigm shift from hypothesis- to data-driven research. Genome-wide profiling efforts gave informative insights into biological processes; however, considering the wealth of variation, the major challenge remains their meaningful interpretation. In particular sequence variation in non-coding contexts is often challenging to interpret. Here, data integration approaches for the identification of functional genetic variability represent a likely solution. Exemplary, functional linkage analysis integrating genotype and expression data determined regulatory quantitative trait loci (QTL and proposed causal relationships. In addition to gene expression, epigenetic regulation and specifically DNA methylation was established as highly valuable surrogate mark for functional variance of the genetic code. Epigenetic modification served as powerful mediator trait to elucidate mechanisms forming phenotypes in health and disease. Particularly, integrative studies of genetic and DNA methylation data yet guided interpretation strategies of risk genotypes, but also proved their value for physiological traits, such as natural human variation and aging. This Perspective seeks to illustrate the power of data integration in the genomic era exemplified by DNA methylation quantitative trait loci (meQTLs. However, the model is further extendable to virtually all traceable molecular traits.

  11. Current Views on Genetics and Epigenetics of Cholesterol Gallstone Disease

    Directory of Open Access Journals (Sweden)

    Agostino Di Ciaula

    2013-01-01

    Full Text Available Cholesterol gallstone disease, one of the commonest digestive diseases in western countries, is induced by an imbalance in cholesterol metabolism, which involves intestinal absorption, hepatic biosynthesis, and biliary output of cholesterol, and its conversion to bile acids. Several components of the metabolic syndrome (e.g., obesity, type 2 diabetes, dyslipidemia, and hyperinsulinemia are also well-known risk factors for gallstones, suggesting the existence of interplay between common pathophysiological pathways influenced by insulin resistance, genetic, epigenetic, and environmental factors. Cholesterol gallstones may be enhanced, at least in part, by the abnormal expression of a set of the genes that affect cholesterol homeostasis and lead to insulin resistance. Additionally, epigenetic mechanisms (mainly DNA methylation, histone acetylation/deacetylation, and noncoding microRNAs may modify gene expression in the absence of an altered DNA sequence, in response to different lithogenic environmental stimuli, such as diet, lifestyle, pollutants, also occurring in utero before birth. In this review, we will comment on various steps of the pathogenesis of cholesterol gallstones and interaction between environmental and genetic factors. The epigenomic approach may offer new options for therapy of gallstones and better possibilities for primary prevention in subjects at risk.

  12. Towards a systemic paradigm in carcinogenesis: linking epigenetics and genetics.

    Science.gov (United States)

    Burgio, Ernesto; Migliore, Lucia

    2015-04-01

    For at least 30 years cancer has been defined as a genetic disease and explained by the so-called somatic mutation theory (SMT), which has dominated the carcinogenesis field. Criticism of the SMT has recently greatly increased, although still not enough to force all SMT supporters to recognize its limits. Various researchers point out that cancer appears to be a complex process concerning a whole tissue; and that genomic mutations, although variably deleterious and unpredictably important in determining the establishment of the neoplastic phenotype, are not the primary origin for a malignant neoplasia. We attempt to describe the inadequacies of the SMT and demonstrate that epigenetics is a more logical cause of carcinogenesis. Many previous models of carcinogenesis fall into two classes: (i) in which some biological changes inside cells alone lead to malignancy; and (ii) requiring changes in stroma/extracellular matrix. We try to make clear that in the (ii) model genomic instability is induced by persistent signals coming from the microenvironment, provoking epigenetic and genetic modifications in tissue stem cells that can lead to cancer. In this perspective, stochastic mutations of DNA are a critical by-product rather then the primary cause of cancer. Indirect support for such model of carcinogenesis comes from the in vitro and vivo experiments showing apparent 'reversion' of cancer phenotypes obtained via physiological factors of cellular differentiation (cytokines and other signaling molecules) or drugs, even if the key mutations are not 'reversed'.

  13. Genetic and epigenetic mechanisms of epilepsy: a review

    Directory of Open Access Journals (Sweden)

    Chen T

    2017-07-01

    Full Text Available Tian Chen,1,* Mohan Giri,2,* Zhenyi Xia,3 Yadu Nanda Subedi,2 Yan Li1 1Department of Health Management Center, Chongqing Three Gorges Central Hospital, Chongqing, People’s Republic of China; 2National Center for Rheumatic Diseases, Ratopul, Gaushala, Kathmandu, Nepal; 3Department of Thoracic Surgery, Chongqing Three Gorges Central Hospital, Chongqing, People’s Republic of China *These authors contributed equally to this work Abstract: Epilepsy is a common episodic neurological disorder or condition characterized by recurrent epileptic seizures, and genetics seems to play a key role in its etiology. Early linkage studies have localized multiple loci that may harbor susceptibility genes to epilepsy, and mutational analyses have detected a number of mutations involved in both ion channel and nonion channel genes in patients with idiopathic epilepsy. Genome-wide studies of epilepsy have found copy number variants at 2q24.2-q24.3, 7q11.22, 15q11.2-q13.3, and 16p13.11-p13.2, some of which disrupt multiple genes, such as NRXN1, AUTS2, NLGN1, CNTNAP2, GRIN2A, PRRT2, NIPA2, and BMP5, implicated for neurodevelopmental disorders, including intellectual disability and autism. Unfortunately, only a few common genetic variants have been associated with epilepsy. Recent exome-sequencing studies have found some genetic mutations, most of which are located in nonion channel genes such as the LGI1, PRRT2, EFHC1, PRICKLE, RBFOX1, and DEPDC5 and in probands with rare forms of familial epilepsy, and some of these genes are involved with the neurodevelopment. Since epigenetics plays a role in neuronal function from embryogenesis and early brain development to tissue-specific gene expression, epigenetic regulation may contribute to the genetic mechanism of neurodevelopment through which a gene and the environment interacting with each other affect the development of epilepsy. This review focused on the analytic tools used to identify epilepsy and then provided a

  14. Type 2 Diabetes Mellitus and Cardiovascular Disease: Genetic and Epigenetic Links

    Directory of Open Access Journals (Sweden)

    Salvatore De Rosa

    2018-01-01

    Full Text Available Type 2 diabetes mellitus (DM is a common metabolic disorder predisposing to diabetic cardiomyopathy and atherosclerotic cardiovascular disease (CVD, which could lead to heart failure through a variety of mechanisms, including myocardial infarction and chronic pressure overload. Pathogenetic mechanisms, mainly linked to hyperglycemia and chronic sustained hyperinsulinemia, include changes in metabolic profiles, intracellular signaling pathways, energy production, redox status, increased susceptibility to ischemia, and extracellular matrix remodeling. The close relationship between type 2 DM and CVD has led to the common soil hypothesis, postulating that both conditions share common genetic and environmental factors influencing this association. However, although the common risk factors of both CVD and type 2 DM, such as obesity, insulin resistance, dyslipidemia, inflammation, and thrombophilia, can be identified in the majority of affected patients, less is known about how these factors influence both conditions, so that efforts are still needed for a more comprehensive understanding of this relationship. The genetic, epigenetic, and environmental backgrounds of both type 2 DM and CVD have been more recently studied and updated. However, the underlying pathogenetic mechanisms have seldom been investigated within the broader shared background, but rather studied in the specific context of type 2 DM or CVD, separately. As the precise pathophysiological links between type 2 DM and CVD are not entirely understood and many aspects still require elucidation, an integrated description of the genetic, epigenetic, and environmental influences involved in the concomitant development of both diseases is of paramount importance to shed new light on the interlinks between type 2 DM and CVD. This review addresses the current knowledge of overlapping genetic and epigenetic aspects in type 2 DM and CVD, including microRNAs and long non-coding RNAs, whose

  15. Salmon and steelhead genetics and genomics - Epigenetic and genomic variation in salmon and steelhead

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Conduct analyses of epigenetic and genomic variation in Chinook salmon and steelhead to determine influence on phenotypic expression of life history traits. Genetic,...

  16. Genetic and epigenetic differences associated with environmental gradients in replicate populations of two salt marsh perennials

    NARCIS (Netherlands)

    Foust, C.M.; Preite, V.; Schrey, A.W.; Alvarez, M.; Robertson, M.H.; Verhoeven, K.J.F.; Richards, Christina L.

    2016-01-01

    While traits and trait plasticity are partly genetically based, investigating epigenetic mechanisms may provide more nuanced understanding of the mechanisms underlying response to environment. Using AFLP and methylation-sensitive AFLP, we tested the hypothesis that differentiation to habitats along

  17. The various aspects of genetic and epigenetic toxicology: testing methods and clinical applications.

    Science.gov (United States)

    Ren, Ning; Atyah, Manar; Chen, Wan-Yong; Zhou, Chen-Hao

    2017-05-22

    Genotoxicity refers to the ability of harmful substances to damage genetic information in cells. Being exposed to chemical and biological agents can result in genomic instabilities and/or epigenetic alterations, which translate into a variety of diseases, cancer included. This concise review discusses, from both a genetic and epigenetic point of view, the current detection methods of different agents' genotoxicity, along with their basic and clinical relation to human cancer, chemotherapy, germ cells and stem cells.

  18. Genetic and epigenetic markers in colorectal cancer screening: recent advances.

    Science.gov (United States)

    Singh, Manish Pratap; Rai, Sandhya; Suyal, Shradha; Singh, Sunil Kumar; Singh, Nand Kumar; Agarwal, Akash; Srivastava, Sameer

    2017-07-01

    Colorectal cancer (CRC) is a heterogenous disease which develops from benign intraepithelial lesions known as adenomas to malignant carcinomas. Acquired alterations in Wnt signaling, TGFβ, MAPK pathway genes and clonal propagation of altered cells are responsible for this transformation. Detection of adenomas or early stage cancer in asymptomatic patients and better prognostic and predictive markers is important for improving the clinical management of CRC. Area covered: In this review, the authors have evaluated the potential of genetic and epigenetic alterations as markers for early detection, prognosis and therapeutic predictive potential in the context of CRC. We have discussed molecular heterogeneity present in CRC and its correlation to prognosis and response to therapy. Expert commentary: Molecular marker based CRC screening methods still fail to gain trust of clinicians. Invasive screening methods, molecular heterogeneity, chemoresistance and low quality test samples are some key challenges which need to be addressed in the present context. New sequencing technologies and integrated omics data analysis of individual or population cohort results in GWAS. MPE studies following a GWAS could be future line of research to establish accurate correlations between CRC and its risk factors. This strategy would identify most reliable biomarkers for CRC screening and management.

  19. Using induced pluripotent stem cells to explore genetic and epigenetic variation associated with Alzheimer's disease.

    Science.gov (United States)

    Imm, Jennifer; Kerrigan, Talitha L; Jeffries, Aaron; Lunnon, Katie

    2017-11-01

    It is thought that both genetic and epigenetic variation play a role in Alzheimer's disease initiation and progression. With the advent of somatic cell reprogramming into induced pluripotent stem cells it is now possible to generate patient-derived cells that are able to more accurately model and recapitulate disease. Furthermore, by combining this with recent advances in (epi)genome editing technologies, it is possible to begin to examine the functional consequence of previously nominated genetic variants and infer epigenetic causality from recently identified epigenetic variants. In this review, we explore the role of genetic and epigenetic variation in Alzheimer's disease and how the functional relevance of nominated loci can be investigated using induced pluripotent stem cells and (epi)genome editing techniques.

  20. Epigenetic differentiation and relationship to adaptive genetic divergence in discrete populations of the violet Viola cazorlensis.

    Science.gov (United States)

    Herrera, Carlos M; Bazaga, Pilar

    2010-08-01

    *In plants, epigenetic variations based on DNA methylation are often heritable and could influence the course of evolution. Before this hypothesis can be assessed, fundamental questions about epigenetic variation remain to be addressed in a real-world context, including its magnitude, structuring within and among natural populations, and autonomy in relation to the genetic context. *Extent and patterns of cytosine methylation, and the relationship to adaptive genetic divergence between populations, were investigated for wild populations of the southern Spanish violet Viola cazorlensis (Violaceae) using the methylation-sensitive amplified polymorphism (MSAP) technique, a modification of the amplified fragment length polymorphism method (AFLP) based on the differential sensitivity of isoschizomeric restriction enzymes to site-specific cytosine methylation. *The genome of V. cazorlensis plants exhibited extensive levels of methylation, and methylation-based epigenetic variation was structured into distinct between- and within- population components. Epigenetic differentiation of populations was correlated with adaptive genetic divergence revealed by a Bayesian population-genomic analysis of AFLP data. Significant associations existed at the individual genome level between adaptive AFLP loci and the methylation state of methylation-susceptible MSAP loci. *Population-specific, divergent patterns of correlated selection on epigenetic and genetic individual variation could account for the coordinated epigenetic-genetic adaptive population differentiation revealed by this study.

  1. Genetic and epigenetic regulation of YKL-40 in childhood.

    Science.gov (United States)

    Guerra, Stefano; Melén, Erik; Sunyer, Jordi; Xu, Cheng-Jian; Lavi, Iris; Benet, Marta; Bustamante, Mariona; Carsin, Anne-Elie; Dobaño, Carlota; Guxens, Mònica; Tischer, Christina; Vrijheid, Martine; Kull, Inger; Bergström, Anna; Kumar, Ashish; Söderhäll, Cilla; Gehring, Ulrike; Dijkstra, Dorieke J; van der Vlies, Pieter; Wickman, Magnus; Bousquet, Jean; Postma, Dirkje S; Anto, Josep M; Koppelman, Gerard H

    2018-03-01

    Circulating levels of the chitinase-like protein YKL-40 are influenced by genetic variation in its encoding gene (chitinase 3-like 1 [CHI3L1]) and are increased in patients with several diseases, including asthma. Epigenetic regulation of circulating YKL-40 early in life is unknown. We sought to determine (1) whether methylation levels at CHI3L1 CpG sites mediate the association of CHI3L1 single nucleotide polymorphisms (SNPs) with YKL-40 levels in the blood and (2) whether these biomarkers (CHI3L1 SNPs, methylation profiles, and YKL-40 levels) are associated with asthma in early childhood. We used data from up to 2405 participants from the Spanish Infancia y Medio Ambiente; the Swedish Barn/Children, Allergy, Milieu, Stockholm, Epidemiological survey; and the Dutch Prevention and Incidence of Asthma and Mite Allergy birth cohorts. Associations between 68 CHI3L1 SNPs, methylation levels at 14 CHI3L1 CpG sites in whole-blood DNA, and circulating YKL-40 levels at 4 years of age were tested by using correlation analysis, multivariable regression, and mediation analysis. Each of these biomarkers was also tested for association with asthma at 4 years of age by using multivariable logistic regression. YKL-40 levels were significantly associated with 7 SNPs and with methylation at 5 CpG sites. Consistent associations between these 7 SNPs (particularly rs10399931 and rs4950928) and 5 CpG sites were observed. Alleles linked to lower YKL-40 levels were associated with higher methylation levels. Participants with high YKL-40 levels (defined as the highest YKL-40 tertile) had increased odds for asthma compared with subjects with low YKL-40 levels (meta-analyzed adjusted odds ratio, 1.90 [95% CI, 1.08-3.36]). In contrast, neither SNPs nor methylation levels at CpG sites in CHI3L1 were associated with asthma. The effects of CHI3L1 genetic variation on circulating YKL-40 levels are partly mediated by methylation profiles. In our study YKL-40 levels, but not CHI3L1 SNPs or

  2. Recent Advances in Human Genetics and Epigenetics of Adiposity: Pathway to Precision Medicine?

    Science.gov (United States)

    Fall, Tove; Mendelson, Michael; Speliotes, Elizabeth K

    2017-05-01

    Obesity is a heritable trait that contributes to substantial global morbidity and mortality. Here, we summarize findings from the past decade of genetic and epigenetic research focused on unravelling the underpinnings of adiposity. More than 140 genetic regions now are known to influence adiposity traits. The genetics of general adiposity, as measured by body mass index, and that of abdominal obesity, as measured by waist-to-hip ratio, have distinct biological backgrounds. Gene expression associated with general adiposity is enriched in the nervous system. In contrast, genes associated with abdominal adiposity function in adipose tissue. Recent population-based epigenetic analyses have highlighted additional distinct loci. We discuss how associated genetic variants can lead to understanding causal mechanisms, and to disentangling reverse causation in epigenetic analyses. Discoveries emerging from population genomics are identifying new disease markers and potential novel drug targets to better define and combat obesity and related diseases. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    Maki, Katherine A; DeVon, Holli A

    2018-04-01

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

  4. Merging data from genetic and epigenetic approaches to better understand autistic spectrum disorder.

    Science.gov (United States)

    Grayson, Dennis R; Guidotti, Alessandro

    2016-01-01

    Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that is characterized by a wide range of cognitive and behavioral abnormalities. Genetic research has identified large numbers of genes that contribute to ASD phenotypes. There is compelling evidence that environmental factors contribute to ASD through influences that differentially impact the brain through epigenetic mechanisms. Both genetic mutations and epigenetic influences alter gene expression in different cell types of the brain. Mutations impact the expression of large numbers of genes and also have downstream consequences depending on specific pathways associated with the mutation. Environmental factors impact the expression of sets of genes by altering methylation/hydroxymethylation patterns, local histone modification patterns and chromatin remodeling. Herein, we discuss recent developments in the research of ASD with a focus on epigenetic pathways as a complement to current genetic screening.

  5. Epigenetics of Autism Spectrum Disorder.

    Science.gov (United States)

    Siu, Michelle T; Weksberg, Rosanna

    2017-01-01

    Autism spectrum disorder (ASD), one of the most common childhood neurodevelopmental disorders (NDDs), is diagnosed in 1 of every 68 children. ASD is incredibly heterogeneous both clinically and aetiologically. The etiopathogenesis of ASD is known to be complex, including genetic, environmental and epigenetic factors. Normal epigenetic marks modifiable by both genetics and environmental exposures can result in epigenetic alterations that disrupt the regulation of gene expression, negatively impacting biological pathways important for brain development. In this chapter we aim to summarize some of the important literature that supports a role for epigenetics in the underlying molecular mechanism of ASD. We provide evidence from work in genetics, from environmental exposures and finally from more recent studies aimed at directly determining ASD-specific epigenetic patterns, focusing mainly on DNA methylation (DNAm). Finally, we briefly discuss some of the implications of current research on potential epigenetic targets for therapeutics and novel avenues for future work.

  6. Integument pattern formation involves genetic and epigenetic controls: feather arrays simulated by digital hormone models.

    Science.gov (United States)

    Jiang, Ting-Xin; Widelitz, Randall B; Shen, Wei-Min; Will, Peter; Wu, Da-Yu; Lin, Chih-Min; Jung, Han-Sung; Chuong, Cheng-Ming

    2004-01-01

    Pattern formation is a fundamental morphogenetic process. Models based on genetic and epigenetic control have been proposed but remain controversial. Here we use feather morphogenesis for further evaluation. Adhesion molecules and/or signaling molecules were first expressed homogenously in feather tracts (restrictive mode, appear earlier) or directly in bud or inter-bud regions ( de novo mode, appear later). They either activate or inhibit bud formation, but paradoxically colocalize in the bud. Using feather bud reconstitution, we showed that completely dissociated cells can reform periodic patterns without reference to previous positional codes. The patterning process has the characteristics of being self-organizing, dynamic and plastic. The final pattern is an equilibrium state reached by competition, and the number and size of buds can be altered based on cell number and activator/inhibitor ratio, respectively. We developed a Digital Hormone Model which consists of (1) competent cells without identity that move randomly in a space, (2) extracellular signaling hormones which diffuse by a reaction-diffusion mechanism and activate or inhibit cell adhesion, and (3) cells which respond with topological stochastic actions manifested as changes in cell adhesion. Based on probability, the results are cell clusters arranged in dots or stripes. Thus genetic control provides combinational molecular information which defines the properties of the cells but not the final pattern. Epigenetic control governs interactions among cells and their environment based on physical-chemical rules (such as those described in the Digital Hormone Model). Complex integument patterning is the sum of these two components of control and that is why integument patterns are usually similar but non-identical. These principles may be shared by other pattern formation processes such as barb ridge formation, fingerprints, pigmentation patterning, etc. The Digital Hormone Model can also be applied to

  7. Mechanistic modelling of genetic and epigenetic events in radiation carcinogenesis

    International Nuclear Information System (INIS)

    Andreev, S. G.; Eidelman, Y. A.; Salnikov, I. V.; Khvostunov, I. K.

    2006-01-01

    Methodological problems arise on the way of radiation carcinogenesis modelling with the incorporation of radiobiological and cancer biology mechanistic data. The results of biophysical modelling of different endpoints [DNA DSB induction, repair, chromosome aberrations (CA) and cell proliferation] are presented and applied to the analysis of RBE-LET relationships for radiation-induced neoplastic transformation (RINT) of C3H/10T1/2 cells in culture. Predicted values for some endpoints correlate well with the data. It is concluded that slowly repaired DSB clusters, as well as some kind of CA, may be initiating events for RINT. As an alternative interpretation, it is possible that DNA damage can induce RINT indirectly via epigenetic process. A hypothetical epigenetic pathway for RINT is discussed. (authors)

  8. Progressive erosion of genetic and epigenetic variation in callus-derived cocoa (Theobroma cacao) plants.

    Science.gov (United States)

    Rodríguez López, Carlos M; Wetten, Andrew C; Wilkinson, Michael J

    2010-06-01

    *Relatively little is known about the timing of genetic and epigenetic forms of somaclonal variation arising from callus growth. We surveyed for both types of change in cocoa (Theobroma cacao) plants regenerated from calli of various ages, and also between tissues from the source trees. *For genetic change, we used 15 single sequence repeat (SSR) markers from four source trees and from 233 regenerated plants. For epigenetic change, we used 386 methylation-sensitive amplified polymorphism (MSAP) markers on leaf and explant (staminode) DNA from two source trees and on leaf DNA from 114 regenerants. *Genetic variation within source trees was limited to one slippage mutation in one leaf. Regenerants were far more variable, with 35% exhibiting at least one mutation. Genetic variation initially accumulated with culture age but subsequently declined. MSAP (epigenetic) profiles diverged between leaf and staminode samples from source trees. Multivariate analysis revealed that leaves from regenerants occupied intermediate eigenspace between leaves and staminodes of source plants but became progressively more similar to source tree leaves with culture age. *Statistical analysis confirmed this rather counterintuitive finding that leaves of 'late regenerants' exhibited significantly less genetic and epigenetic divergence from source leaves than those exposed to short periods of callus growth.

  9. HPA AXIS RELATED GENES AND RESPONSE TO PSYCHOLOGICAL THERAPIES: GENETICS AND EPIGENETICS

    NARCIS (Netherlands)

    Roberts, Susanna; Keers, Robert; Lester, Kathryn J.; Coleman, Jonathan R. I.; Breen, Gerome; Arendt, Kristian; Blatter-Meunier, Judith; Cooper, Peter; Creswell, Cathy; Fjermestad, Krister; Havik, Odd E.; Herren, Chantal; Hogendoorn, Sanne M.; Hudson, Jennifer L.; Krause, Karen; Lyneham, Heidi J.; Morris, Talia; Nauta, Maaike; Rapee, Ronald M.; Rey, Yasmin; Schneider, Silvia; Schneider, Sophie C.; Silverman, Wendy K.; Thastum, Mikael; Thirlwall, Kerstin; Waite, Polly; Eley, Thalia C.; Wong, Chloe C. Y.

    2015-01-01

    Hypothalamic-pituitary-adrenal (HPA) axis functioning has been implicated in the development of stress-related psychiatric diagnoses and response to adverse life experiences. This study aimed to investigate the association between genetic and epigenetics in HPA axis and response to cognitive

  10. Genetic and epigenetic similarities and differences between childhood and adult AML

    DEFF Research Database (Denmark)

    Juhl-Christensen, Caroline; Ommen, Hans Beier; Aggerholm, Anni

    2012-01-01

    The biology of acute myeloid leukemia (AML) is complex and includes both genetic and epigenetic aberrations. We addressed the combined consequences of promoter hypermethylation of p15, CDH1, ER, MDR1, and RARB2 and mutation of NPM1, CEBPA, FLT3, and WT1 in a Danish cohort of 70 pediatric and 383...

  11. Grand challenges in evolutionary and population genetics: The importance of integrating epigenetics, genomics, modeling, and experimentation

    Science.gov (United States)

    Samuel A. Cushman

    2014-01-01

    This is a time of explosive growth in the fields of evolutionary and population genetics, with whole genome sequencing and bioinformatics driving a transformative paradigm shift (Morozova and Marra, 2008). At the same time, advances in epigenetics are thoroughly transforming our understanding of evolutionary processes and their implications for populations, species and...

  12. Investigating the genetic and epigenetic basis of big biological questions with the parthenogenetic marbled crayfish: A review and perspectives.

    Science.gov (United States)

    Vogt, Gunter

    2018-03-01

    In the last 15 years, considerable attempts have been undertaken to develop the obligately parthenogenetic marbled crayfish Procambarus virginalis as a new model in biology. Its main advantage is the production of large numbers of offspring that are genetically identical to the mother, making this crustacean particularly suitable for research in epigenetics. Now, a draft genome, transcriptome and genome-wide methylome are available opening new windows for research. In this article, I summarize the biological advantages and genomic and epigenetic features of marbled crayfish and, based on first promising data, discuss what this new model could contribute to answering of ''big'' biological questions. Genome mining is expected to reveal new insights into the genetic specificities of decapod crustaceans, the genetic basis of arthropod reproduction, moulting and immunity, and more general topics such as the genetic underpinning of adaptation to fresh water, omnivory, biomineralization, sexual system change, behavioural variation, clonal genome evolution, and resistance to cancer. Epigenetic investigations with the marbled crayfish can help clarifying the role of epigenetic mechanisms in gene regulation, tissue specification, adult stem cell regulation, cell ageing, organ regeneration and disease susceptibility. Marbled crayfish is further suitable to elucidate the relationship between genetic and epigenetic variation, the transgenerational inheritance of epigenetic signatures and the contribution of epigenetic phenotype variation to the establishment of social hierarchies, environmental adaptation and speciation. These issues can be tackled by experiments with highly standardized laboratory lineages, comparison of differently adapted wild populations and the generation of genetically and epigenetically edited strains.

  13. Toxic stress history and hypothalamic-pituitary-adrenal axis function in a social stress task: Genetic and epigenetic factors.

    Science.gov (United States)

    Lapp, Hannah E; Ahmed, Sarah; Moore, Celia L; Hunter, Richard G

    2018-02-21

    Histories of early life stress (ELS) or social discrimination can reach levels of severity characterized as toxic to mental and physical health. Such toxic social stress during development has been linked to altered acute hypothalamic-pituitary-adrenal (HPA) response to social stress in adulthood. However, there are important individual differences in the size and direction of these effects. We explored developmental, genetic, epigenetic, and contextual sources of individual differences in the relationship between ELS, discrimination, and adult responses to acute social stress in a standard laboratory test. Additional measures included perceived status, social support, background activity of HPA axis, and genetic variants in aspects of the stress response system. Participants (n = 90) answered questions about historical and ongoing stress, provided a DNA sample to examine genetic polymorphisms and epigenetic marks, and underwent the Trier Social Stress Test (TSST) during which three saliva samples were collected to assess HPA function. Individuals who reported high levels of childhood adversity had a blunted salivary cortisol response to the TSST. Childhood adversity, discrimination experiences, and FKBP5 genotype were found to predict pretest cortisol levels. Following up on recent observations that the glucocorticoid receptor directly interacts with the mitochondrial genome, particularly the NADH dehydrogenase 6 (MT-ND6) gene, individuals who reported high childhood adversity were also found to have higher percent methylation across six CpG sites upstream of MT-ND6. These findings suggest multiple contributions across psychological, genetic, epigenetic, and social domains to vulnerability and resilience in hypothalamic-pituitary-adrenal axis regulation. Further study to examine how these multiple contributors affect developmental endpoints through integrated or independent pathways will be of use. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. DNA Fingerprinting Techniques for the Analysis of Genetic and Epigenetic Alterations in Colorectal Cancer

    OpenAIRE

    Samuelsson, Johanna K.; Alonso, Sergio; Yamamoto, Fumiichiro; Perucho, Manuel

    2010-01-01

    Genetic somatic alterations are fundamental hallmarks of cancer. In addition to point and other small mutations targeting cancer genes, solid tumors often exhibit aneuploidy as well as multiple chromosomal rearrangements of large fragments of the genome. Whether somatic chromosomal alterations and aneuploidy are a driving force or a mere consequence of tumorigenesis remains controversial. Recently it became apparent that not only genetic but also epigenetic alterations play a major role in ca...

  15. The beginnings of Alzheimer’s disease: A review on inflammatory, mitochondrial, genetic and epigenetic pathways

    Directory of Open Access Journals (Sweden)

    Perna Simone

    2016-01-01

    Full Text Available Alzheimer’s Disease (AD is the most common cause of sporadic dementia, as it affects 60% of cognitive impaired patients; it commonly affects middle and late life, and it is considered an age-related disease. Early-onset familial AD is associated with mutations of the genes encoding amyloid precursor protein (APP, presenilin 1 (PS-1, or PS-2, resulting in the overproduction of amyloid beta-protein. Epidemiological and case-control studies have led to the identification of several risk factors for sporadic AD. The most concrete genetic risk factor for AD is the epsilon4 allele of apolipoprotein E gene (APOE. In addition, several genes such as CTNNA3, GAB2, PVRL2, TOMM40, and APOC1 are known to be the risk factors that contribute to AD pathogenesis. A direct role of interaction between genetic and environmental determinants has been proposed in an epigenetic dynamic for environmental factors operating during the preconceptual, fetal and infant phases of life. Also the the association between mtDNA inherited variants and multifactorial diseases and AD has been investigated by a number of studies that, however, didn’t reach a general consensus on the correlation between mtDNA haplogroups and AD.

  16. Epigenetic variability in the genetically uniform forest tree species Pinus pinea L.

    Directory of Open Access Journals (Sweden)

    Enrique Sáez-Laguna

    Full Text Available There is an increasing interest in understanding the role of epigenetic variability in forest species and how it may contribute to their rapid adaptation to changing environments. In this study we have conducted a genome-wide analysis of cytosine methylation pattern in Pinus pinea, a species characterized by very low levels of genetic variation and a remarkable degree of phenotypic plasticity. DNA methylation profiles of different vegetatively propagated trees from representative natural Spanish populations of P. pinea were analyzed with the Methylation Sensitive Amplified Polymorphism (MSAP technique. A high degree of cytosine methylation was detected (64.36% of all scored DNA fragments. Furthermore, high levels of epigenetic variation were observed among the studied individuals. This high epigenetic variation found in P. pinea contrasted with the lack of genetic variation based on Amplified Fragment Length Polymorphism (AFLP data. In this manner, variable epigenetic markers clearly discriminate individuals and differentiates two well represented populations while the lack of genetic variation revealed with the AFLP markers fail to differentiate at both, individual or population levels. In addition, the use of different replicated trees allowed identifying common polymorphic methylation sensitive MSAP markers among replicates of a given propagated tree. This set of MSAPs allowed discrimination of the 70% of the analyzed trees.

  17. Epigenetic variability in the genetically uniform forest tree species Pinus pinea L.

    Science.gov (United States)

    Sáez-Laguna, Enrique; Guevara, María-Ángeles; Díaz, Luis-Manuel; Sánchez-Gómez, David; Collada, Carmen; Aranda, Ismael; Cervera, María-Teresa

    2014-01-01

    There is an increasing interest in understanding the role of epigenetic variability in forest species and how it may contribute to their rapid adaptation to changing environments. In this study we have conducted a genome-wide analysis of cytosine methylation pattern in Pinus pinea, a species characterized by very low levels of genetic variation and a remarkable degree of phenotypic plasticity. DNA methylation profiles of different vegetatively propagated trees from representative natural Spanish populations of P. pinea were analyzed with the Methylation Sensitive Amplified Polymorphism (MSAP) technique. A high degree of cytosine methylation was detected (64.36% of all scored DNA fragments). Furthermore, high levels of epigenetic variation were observed among the studied individuals. This high epigenetic variation found in P. pinea contrasted with the lack of genetic variation based on Amplified Fragment Length Polymorphism (AFLP) data. In this manner, variable epigenetic markers clearly discriminate individuals and differentiates two well represented populations while the lack of genetic variation revealed with the AFLP markers fail to differentiate at both, individual or population levels. In addition, the use of different replicated trees allowed identifying common polymorphic methylation sensitive MSAP markers among replicates of a given propagated tree. This set of MSAPs allowed discrimination of the 70% of the analyzed trees.

  18. DNA fingerprinting techniques for the analysis of genetic and epigenetic alterations in colorectal cancer.

    Science.gov (United States)

    Samuelsson, Johanna K; Alonso, Sergio; Yamamoto, Fumiichiro; Perucho, Manuel

    2010-11-10

    Genetic somatic alterations are fundamental hallmarks of cancer. In addition to point and other small mutations targeting cancer genes, solid tumors often exhibit aneuploidy as well as multiple chromosomal rearrangements of large fragments of the genome. Whether somatic chromosomal alterations and aneuploidy are a driving force or a mere consequence of tumorigenesis remains controversial. Recently it became apparent that not only genetic but also epigenetic alterations play a major role in carcinogenesis. Epigenetic regulation mechanisms underlie the maintenance of cell identity crucial for development and differentiation. These epigenetic regulatory mechanisms have been found substantially altered during cancer development and progression. In this review, we discuss approaches designed to analyze genetic and epigenetic alterations in colorectal cancer, especially DNA fingerprinting approaches to detect changes in DNA copy number and methylation. DNA fingerprinting techniques, despite their modest throughput, played a pivotal role in significant discoveries in the molecular basis of colorectal cancer. The aim of this review is to revisit the fingerprinting technologies employed and the oncogenic processes that they unveiled. 2010 Elsevier B.V. All rights reserved.

  19. Genetic and epigenetic divergence between disturbed and undisturbed subpopulations of a Mediterranean shrub: a 20-year field experiment.

    Science.gov (United States)

    Herrera, Carlos M; Bazaga, Pilar

    2016-06-01

    Little is known on the potential of ecological disturbance to cause genetic and epigenetic changes in plant populations. We take advantage of a long-term field experiment initiated in 1986 to study the demography of the shrub Lavandula latifolia , and compare genetic and epigenetic characteristics of plants in two adjacent subplots, one experimentally disturbed and one left undisturbed, 20 years after disturbance. Experimental setup was comparable to an unreplicated 'Before-After-Control-Impact' (BACI) design where a single pair of perturbed and control areas were compared. When sampled in 2005, plants in the two subplots had roughly similar ages, but they had established in contrasting environments: dense conspecific population ('Undisturbed' subpopulation) versus open area with all conspecifics removed ('Disturbed' subpopulation). Plants were characterized genetically and epigenetically using amplified fragment length polymorphism (AFLP) and two classes of methylation-sensitive AFLP (MSAP) markers. Subpopulations were similar in genetic diversity but differed in epigenetic diversity and multilocus genetic and epigenetic characteristics. Epigenetic divergence between subpopulations was statistically unrelated to genetic divergence. Bayesian clustering revealed an abrupt linear boundary between subpopulations closely coincident with the arbitrary demarcation line between subplots drawn 20 years back, which supports that genetic and epigenetic divergence between subpopulations was caused by artificial disturbance. There was significant fine-scale spatial structuring of MSAP markers in both subpopulations, which in the Undisturbed one was indistinguishable from that of AFLP markers. Genetic differences between subpopulations could be explained by divergent selection alone, while the concerted action of divergent selection and disturbance-driven appearance of new methylation variants in the Disturbed subpopulation is proposed to explain epigenetic differences. This

  20. New insights in oncology: Epi-genetics and cancer stem cells

    International Nuclear Information System (INIS)

    Krutovskikh, V.; Partensky, C.

    2011-01-01

    Cancer is a multi-etiologic, multistage disease with a prevalent genetic component, which happens when a large number of genes, critical for cell growth, death, differentiation, migration, and metabolic plasticity are altered irreversibly, so as to either 'gain' (oncogenes) or 'lose' (tumour suppressors) their function. Recent discoveries have revealed the previously underestimated etiologic importance of multiple epigenetic, that is to say, reversible factors (histone modifications, DNA methylation, non-coding RNA) involved in the transcriptional and post-transcriptional regulation of proteins, indispensable for the control of cancerous phenotype. Stable alterations of epigenetic machinery ('epi-mutations') turn out to play a critical role at different steps of carcinogenesis. In addition, due to substantial recent progress in stem cell biology, the new concept of cancer stem cells has emerged. This, along with newly discovered epigenetic cancer mechanisms, gives rise to a hope to overcome radio- and chemo-resistance and to eradicate otherwise incurable neoplasms. (authors)

  1. Genetic and Epigenetic Mechanisms That Maintain Hematopoietic Stem Cell Function

    Science.gov (United States)

    Kosan, Christian; Godmann, Maren

    2016-01-01

    All hematopoiesis cells develop from multipotent progenitor cells. Hematopoietic stem cells (HSC) have the ability to develop into all blood lineages but also maintain their stemness. Different molecular mechanisms have been identified that are crucial for regulating quiescence and self-renewal to maintain the stem cell pool and for inducing proliferation and lineage differentiation. The stem cell niche provides the microenvironment to keep HSC in a quiescent state. Furthermore, several transcription factors and epigenetic modifiers are involved in this process. These create modifications that regulate the cell fate in a more or less reversible and dynamic way and contribute to HSC homeostasis. In addition, HSC respond in a unique way to DNA damage. These mechanisms also contribute to the regulation of HSC function and are essential to ensure viability after DNA damage. How HSC maintain their quiescent stage during the entire life is still matter of ongoing research. Here we will focus on the molecular mechanisms that regulate HSC function. PMID:26798358

  2. From genetics and epigenetics to the future of precision treatment for obesity.

    Science.gov (United States)

    Sun, Xulong; Li, Pengzhou; Yang, Xiangwu; Li, Weizheng; Qiu, Xianjie; Zhu, Shaihong

    2017-11-01

    Obesity has become a major global health problem, epitomized by excess accumulation of body fat resulting from an imbalance between energy intake and expenditure. The treatments for obesity range from modified nutrition and additional physical activity, to drugs or surgery. But the curative effect of each method seems to vary between individuals. With progress in the genetics and epigenetics of obesity, personalization of the clinical management of obesity may be at our doorstep. This review presents an overview of our current understanding of the genetics and epigenetics of obesity and how these findings influence responses to treatments. As bariatric surgery is the most effective long-term treatment for morbid obesity, we pay special attention to the association between genetic factors and clinical outcomes of bariatric surgery. Finally, we discuss the prospects for precision obesity treatment.

  3. An integrated epigenetic and genetic analysis of DNA methyltransferase genes (DNMTs) in tumor resistant and susceptible chicken lines

    Science.gov (United States)

    Both epigenetic alterations and genetic variations play essential roles in tumorigenesis. The epigenetic modification of DNA methylation is catalyzed and maintained by the DNA methyltransferases (DNMT3a, DNMT3b and DNMT1). DNA mutations and DNA methylation profiles of DNMTs themselves and their rela...

  4. Genet-specific DNA methylation probabilities detected in a spatial epigenetic analysis of a clonal plant population.

    Directory of Open Access Journals (Sweden)

    Kiwako S Araki

    Full Text Available In sessile organisms such as plants, spatial genetic structures of populations show long-lasting patterns. These structures have been analyzed across diverse taxa to understand the processes that determine the genetic makeup of organismal populations. For many sessile organisms that mainly propagate via clonal spread, epigenetic status can vary between clonal individuals in the absence of genetic changes. However, fewer previous studies have explored the epigenetic properties in comparison to the genetic properties of natural plant populations. Here, we report the simultaneous evaluation of the spatial structure of genetic and epigenetic variation in a natural population of the clonal plant Cardamine leucantha. We applied a hierarchical Bayesian model to evaluate the effects of membership of a genet (a group of individuals clonally derived from a single seed and vegetation cover on the epigenetic variation between ramets (clonal plants that are physiologically independent individuals. We sampled 332 ramets in a 20 m × 20 m study plot that contained 137 genets (identified using eight SSR markers. We detected epigenetic variation in DNA methylation at 24 methylation-sensitive amplified fragment length polymorphism (MS-AFLP loci. There were significant genet effects at all 24 MS-AFLP loci in the distribution of subepiloci. Vegetation cover had no statistically significant effect on variation in the majority of MS-AFLP loci. The spatial aggregation of epigenetic variation is therefore largely explained by the aggregation of ramets that belong to the same genets. By applying hierarchical Bayesian analyses, we successfully identified a number of genet-specific changes in epigenetic status within a natural plant population in a complex context, where genotypes and environmental factors are unevenly distributed. This finding suggests that it requires further studies on the spatial epigenetic structure of natural populations of diverse organisms

  5. Genet-specific DNA methylation probabilities detected in a spatial epigenetic analysis of a clonal plant population.

    Science.gov (United States)

    Araki, Kiwako S; Kubo, Takuya; Kudoh, Hiroshi

    2017-01-01

    In sessile organisms such as plants, spatial genetic structures of populations show long-lasting patterns. These structures have been analyzed across diverse taxa to understand the processes that determine the genetic makeup of organismal populations. For many sessile organisms that mainly propagate via clonal spread, epigenetic status can vary between clonal individuals in the absence of genetic changes. However, fewer previous studies have explored the epigenetic properties in comparison to the genetic properties of natural plant populations. Here, we report the simultaneous evaluation of the spatial structure of genetic and epigenetic variation in a natural population of the clonal plant Cardamine leucantha. We applied a hierarchical Bayesian model to evaluate the effects of membership of a genet (a group of individuals clonally derived from a single seed) and vegetation cover on the epigenetic variation between ramets (clonal plants that are physiologically independent individuals). We sampled 332 ramets in a 20 m × 20 m study plot that contained 137 genets (identified using eight SSR markers). We detected epigenetic variation in DNA methylation at 24 methylation-sensitive amplified fragment length polymorphism (MS-AFLP) loci. There were significant genet effects at all 24 MS-AFLP loci in the distribution of subepiloci. Vegetation cover had no statistically significant effect on variation in the majority of MS-AFLP loci. The spatial aggregation of epigenetic variation is therefore largely explained by the aggregation of ramets that belong to the same genets. By applying hierarchical Bayesian analyses, we successfully identified a number of genet-specific changes in epigenetic status within a natural plant population in a complex context, where genotypes and environmental factors are unevenly distributed. This finding suggests that it requires further studies on the spatial epigenetic structure of natural populations of diverse organisms, particularly for

  6. Genetic and epigenetic factors: Role in male infertility

    Directory of Open Access Journals (Sweden)

    M B Shamsi

    2011-01-01

    Full Text Available Genetic factors contribute upto 15%-30% cases of male infertility. Formation of spermatozoa occurs in a sequential manner with mitotic, meiotic, and postmeiotic differentiation phases each of which is controlled by an intricate genetic program. Genes control a variety of physiologic processes, such as hypothalamus-pituitary-gonadal axis, germ cell development, and differentiation. In the era of assisted reproduction technology, it is important to understand the genetic basis of infertility to provide maximum adapted therapeutics and counseling to the couple.

  7. Epigenetic Alterations in Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Johannes eGräff

    2015-12-01

    Full Text Available Alzheimer’s disease (AD is the major cause of dementia in Western societies. It progresses asymptomatically during decades before being belatedly diagnosed when therapeutic strategies have become unviable. Although several genetic alterations have been associated with AD, the vast majority of AD cases do not show strong genetic underpinnings and are thus considered a consequence of non-genetic factors. Epigenetic mechanisms allow for the integration of long-lasting non-genetic inputs on specific genetic backgrounds, and recently, a growing number of epigenetic alterations in AD have been described. For instance, an accumulation of dysregulated epigenetic mechanisms in aging, the predominant risk factor of AD, might facilitate the onset of the disease. Likewise, mutations in several enzymes of the epigenetic machinery have been associated with neurodegenerative processes that are altered in AD such as impaired learning and memory formation. Genome-wide and locus-specific epigenetic alterations have also been reported, and several epigenetically dysregulated genes validated by independent groups. From these studies, a picture emerges of AD as being associated with DNA hypermethylation and histone deacetylation, suggesting a general repressed chromatin state and epigenetically reduced plasticity in AD. Here we review these recent findings and discuss several technical and methodological considerations that are imperative for their correct interpretation. We also pay particular focus on potential implementations and theoretical frameworks that we expect will help to better direct future studies aimed to unravel the epigenetic participation in AD.

  8. Epigenetic Alterations in Alzheimer's Disease.

    Science.gov (United States)

    Sanchez-Mut, Jose V; Gräff, Johannes

    2015-01-01

    Alzheimer's disease (AD) is the major cause of dementia in Western societies. It progresses asymptomatically during decades before being belatedly diagnosed when therapeutic strategies have become unviable. Although several genetic alterations have been associated with AD, the vast majority of AD cases do not show strong genetic underpinnings and are thus considered a consequence of non-genetic factors. Epigenetic mechanisms allow for the integration of long-lasting non-genetic inputs on specific genetic backgrounds, and recently, a growing number of epigenetic alterations in AD have been described. For instance, an accumulation of dysregulated epigenetic mechanisms in aging, the predominant risk factor of AD, might facilitate the onset of the disease. Likewise, mutations in several enzymes of the epigenetic machinery have been associated with neurodegenerative processes that are altered in AD such as impaired learning and memory formation. Genome-wide and locus-specific epigenetic alterations have also been reported, and several epigenetically dysregulated genes validated by independent groups. From these studies, a picture emerges of AD as being associated with DNA hypermethylation and histone deacetylation, suggesting a general repressed chromatin state and epigenetically reduced plasticity in AD. Here we review these recent findings and discuss several technical and methodological considerations that are imperative for their correct interpretation. We also pay particular focus on potential implementations and theoretical frameworks that we expect will help to better direct future studies aimed to unravel the epigenetic participation in AD.

  9. Investigating the genetic and epigenetic basis of big biological ...

    Indian Academy of Sciences (India)

    Günter Vogt

    2018-02-14

    Feb 14, 2018 ... advantage of producing high numbers of genetically identi- cal offspring. ..... For net culture, small containers should be filled to a water level of about ...... The availability of the genome of marbled crayfish now enables further ...

  10. Genetic and Epigenetic Mechanisms That Maintain Hematopoietic Stem Cell Function

    Directory of Open Access Journals (Sweden)

    Christian Kosan

    2016-01-01

    Full Text Available All hematopoiesis cells develop from multipotent progenitor cells. Hematopoietic stem cells (HSC have the ability to develop into all blood lineages but also maintain their stemness. Different molecular mechanisms have been identified that are crucial for regulating quiescence and self-renewal to maintain the stem cell pool and for inducing proliferation and lineage differentiation. The stem cell niche provides the microenvironment to keep HSC in a quiescent state. Furthermore, several transcription factors and epigenetic modifiers are involved in this process. These create modifications that regulate the cell fate in a more or less reversible and dynamic way and contribute to HSC homeostasis. In addition, HSC respond in a unique way to DNA damage. These mechanisms also contribute to the regulation of HSC function and are essential to ensure viability after DNA damage. How HSC maintain their quiescent stage during the entire life is still matter of ongoing research. Here we will focus on the molecular mechanisms that regulate HSC function.

  11. Tissue culture-induced genetic and epigenetic variation in triticale (× Triticosecale spp. Wittmack ex A. Camus 1927) regenerants.

    Science.gov (United States)

    Machczyńska, Joanna; Zimny, Janusz; Bednarek, Piotr Tomasz

    2015-10-01

    Plant regeneration via in vitro culture can induce genetic and epigenetic variation; however, the extent of such changes in triticale is not yet understood. In the present study, metAFLP, a variation of methylation-sensitive amplified fragment length polymorphism analysis, was used to investigate tissue culture-induced variation in triticale regenerants derived from four distinct genotypes using androgenesis and somatic embryogenesis. The metAFLP technique enabled identification of both sequence and DNA methylation pattern changes in a single experiment. Moreover, it was possible to quantify subtle effects such as sequence variation, demethylation, and de novo methylation, which affected 19, 5.5, 4.5% of sites, respectively. Comparison of variation in different genotypes and with different in vitro regeneration approaches demonstrated that both the culture technique and genetic background of donor plants affected tissue culture-induced variation. The results showed that the metAFLP approach could be used for quantification of tissue culture-induced variation and provided direct evidence that in vitro plant regeneration could cause genetic and epigenetic variation.

  12. Genetic variants of methyl metabolizing enzymes and epigenetic regulators: Associations with promoter CpG island hypermethylation in colorectal cancer

    NARCIS (Netherlands)

    Vogel, S. de; Wouters, K.A.D.; Gottschalk, R.W.H.; Schooten, F.J. van; Goeij, A.F.P.M. de; Bruïne, A.P. de; Goldbohm, R.A.; Brandt, P.A. van den; Weijenberg, M.P.; Engeland, M. van

    2009-01-01

    Aberrant DNA methylation affects carcinogenesis of colorectal cancer. Folate metabolizing enzymes may influence the bioavailability of methyl groups, whereas DNA and histone methyltransferases are involved in epigenetic regulation of gene expression. We studied associations of genetic variants of

  13. Ovarian carcinomas with genetic and epigenetic BRCA1 loss have distinct molecular abnormalities

    International Nuclear Information System (INIS)

    Press, Joshua Z; Smith, Margaret; Spellman, Paul T; Wang, Yuker; Miller, Dianne M; Horsman, Doug; Faham, Malek; Gilks, C Blake; Gray, Joe; Huntsman, David G; De Luca, Alessandro; Boyd, Niki; Young, Sean; Troussard, Armelle; Ridge, Yolanda; Kaurah, Pardeep; Kalloger, Steve E; Blood, Katherine A

    2008-01-01

    Subclassification of ovarian carcinomas can be used to guide treatment and determine prognosis. Germline and somatic mutations, loss of heterozygosity (LOH), and epigenetic events such as promoter hypermethylation can lead to decreased expression of BRCA1/2 in ovarian cancers. The mechanism of BRCA1/2 loss is a potential method of subclassifying high grade serous carcinomas. A consecutive series of 49 ovarian cancers was assessed for mutations status of BRCA1 and BRCA2, LOH at the BRCA1 and BRCA2 loci, methylation of the BRCA1 promoter, BRCA1, BRCA2, PTEN, and PIK3CA transcript levels, PIK3CA gene copy number, and BRCA1, p21, p53, and WT-1 immunohistochemistry. Eighteen (37%) of the ovarian carcinomas had germline or somatic BRCA1 mutations, or epigenetic loss of BRCA1. All of these tumours were high-grade serous or undifferentiated type. None of the endometrioid (n = 5), clear cell (n = 4), or low grade serous (n = 2) carcinomas showed loss of BRCA1, whereas 47% of the 38 high-grade serous or undifferentiated carcinomas had loss of BRCA1. It was possible to distinguish high grade serous carcinomas with BRCA1 mutations from those with epigenetic BRCA1 loss: tumours with BRCA1 mutations typically had decreased PTEN mRNA levels while those with epigenetic loss of BRCA1 had copy number gain of PIK3CA. Overexpression of p53 with loss of p21 expression occurred significantly more frequently in high grade serous carcinomas with epigenetic loss of BRCA1, compared to high grade serous tumors without loss of BRCA1. High grade serous carcinomas can be subclassified into three groups: BRCA1 loss (genetic), BRCA1 loss (epigenetic), and no BRCA1 loss. Tumors in these groups show distinct molecular alterations involving the PI3K/AKT and p53 pathways

  14. Ovarian carcinomas with genetic and epigenetic BRCA1 loss have distinct molecular abnormalities

    Energy Technology Data Exchange (ETDEWEB)

    Gilks, C. Blake; Press, Joshua Z.; De Luca, Alessandro; Boyd, Niki; Young, Sean; Troussard, Armelle; Ridge, Yolanda; Kaurah, Pardeep; Kalloger, Steve E.; Blood, Katherine A.; Smith, Margaret; Spellman, Paul T.; Wang, Yuker; Miller, Dianne M.; Horsman, Doug; Faham, Malek; Gilks, C. Blake; Gray, Joe; Huntsman, David G.

    2008-05-02

    Subclassification of ovarian carcinomas can be used to guide treatment and determine prognosis. Germline and somatic mutations, loss of heterozygosity (LOH), and epigenetic events such as promoter hypermethylation can lead to decreased expression of BRCA1/2 in ovarian cancers. The mechanism of BRCA1/2 loss is a potential method of subclassifying high grade serous carcinomas. A consecutive series of 49 ovarian cancers was assessed for mutations status of BRCA1 and BRCA2, LOH at the BRCA1 and BRCA2 loci, methylation of the BRCA1 promoter, BRCA1, BRCA2, PTEN, and PIK3CA transcript levels, PIK3CA gene copy number, and BRCA1, p21, p53, and WT-1 immunohistochemistry. Eighteen (37%) of the ovarian carcinomas had germline or somatic BRCA1 mutations, or epigenetic loss of BRCA1. All of these tumors were high-grade serous or undifferentiated type. None of the endometrioid (n=5), clear cell (n=4), or low grade serous (n=2) carcinomas showed loss of BRCA1, whereas 47% of the 38 high-grade serous or undifferentiated carcinomas had loss of BRCA1. It was possible to distinguish high grade serous carcinomas with BRCA1 mutations from those with epigenetic BRCA1 loss: tumors with BRCA1 mutations typically had decreased PTEN mRNA levels while those with epigenetic loss of BRCA1 had copy number gain of PIK3CA. Overexpression of p53 with loss of p21 expression occurred significantly more frequently in high grade serous carcinomas with epigenetic loss of BRCA1, compared to high grade serous tumors without loss of BRCA1. High grade serous carcinomas can be subclassified into three groups: BRCA1 loss (genetic), BRCA1 loss (epigenetic), and no BRCA1 loss. Tumors in these groups show distinct molecular alterations involving the PI3K/AKT and p53 pathways.

  15. Ovarian carcinomas with genetic and epigenetic BRCA1 loss havedistinct molecular abnormalities

    Energy Technology Data Exchange (ETDEWEB)

    Press, Joshua Z.; De Luca, Alessandro; Boyd, Niki; Young, Sean; Troussard, Armelle; Ridge, Yolanda; Kaurah, Pardeep; Kalloger, Steve E.; Blood, Katherine A.; Smith, Margaret; Spellman, Paul T.; Wang, Yuker; Miller, Dianne M.; Horsman, Doug; Faham, Malek; Gilks, C. Blake; Gray,Joe; Huntsman, David G.

    2007-07-23

    Subclassification of ovarian carcinomas can be used to guide treatment and determine prognosis. Germline and somatic mutations, loss of heterozygosity (LOH), and epigenetic events such as promoter hypermethylation can lead to decreased expression of BRCA1/2 in ovarian cancers. The mechanism of BRCA1/2 loss is a potential method of subclassifying high grade serous carcinomas. A consecutive series of 49 ovarian cancers was assessed for mutations status of BRCA1 and BRCA2, LOH at the BRCA1 and BRCA2 loci, methylation of the BRCA1 promoter, BRCA1, BRCA2, PTEN, and PIK3CA transcript levels, PIK3CA gene copy number, and BRCA1, p21, p53, and WT-1 immunohistochemistry. Eighteen (37%) of the ovarian carcinomas had germline or somatic BRCA1 mutations, or epigenetic loss of BRCA1. All of these tumors were high-grade serous or undifferentiated type. None of the endometrioid (n = 5), clear cell (n = 4), or low grade serous (n = 2) carcinomas showed loss of BRCA1, whereas 47% of the 38 high-grade serous or undifferentiated carcinomas had loss of BRCA1. It was possible to distinguish high grade serous carcinomas with BRCA1 mutations from those with epigenetic BRCA1 loss: tumors with BRCA1 mutations typically had decreased PTEN mRNA levels while those with epigenetic loss of BRCA1 had copy number gain of PIK3CA. Overexpression of p53 with loss of p21 expression occurred significantly more frequently in high grade serous carcinomas with epigenetic loss of BRCA1, compared to high grade serous tumors without loss of BRCA1. High grade serous carcinomas can be subclassified into three groups: BRCA1 loss (genetic), BRCA1 loss (epigenetic), and no BRCA1 loss. Tumors in these groups show distinct molecular alterations involving the PI3K/AKT and p53 pathways.

  16. Elucidating novel dysfunctional pathways in Alzheimer's disease by integrating loci identified in genetic and epigenetic studies

    Directory of Open Access Journals (Sweden)

    Adam R. Smith

    2016-06-01

    Full Text Available Alzheimer's disease is a complex neurodegenerative disorder. A large number of genome-wide association studies have been performed, which have been supplemented more recently by the first epigenome-wide association studies, leading to the identification of a number of novel loci altered in disease. Twin studies have shown monozygotic twin discordance for Alzheimer's disease (Gatz et al., 2006, leading to the conclusion that a combination of genetic and epigenetic mechanisms is likely to be involved in disease etiology (Lunnon & Mill, 2013. This review focuses on identifying overlapping pathways between published genome-wide association studies and epigenome-wide association studies, highlighting dysfunctional synaptic, lipid metabolism, plasma membrane/cytoskeleton, mitochondrial, and immune cell activation pathways. Identifying common pathways altered in genetic and epigenetic studies will aid our understanding of disease mechanisms and identify potential novel targets for pharmacological intervention.

  17. Biological underpinnings of trauma and post-traumatic stress disorder: focusing on genetics and epigenetics.

    Science.gov (United States)

    Ryan, Joanne; Chaudieu, Isabelle; Ancelin, Marie-Laure; Saffery, Richard

    2016-11-01

    Certain individuals are more susceptible to stress and trauma, as well as the physical and mental health consequences following such exposure, including risk for post-traumatic stress disorder (PTSD). This differing vulnerability is likely to be influenced by genetic predisposition and specific characteristics of the stress itself (nature, intensity and duration), as well as epigenetic mechanisms. In this review we provide an overview of research findings in this field. We highlight some of the key genetic risk factors identified for PTSD, and the evidence that epigenetic processes might play a role in the biological response to trauma, as well as being potential biomarkers of PTSD risk. We also discuss important considerations for future research in this area.

  18. From genetics and epigenetics to the future of precision treatment for obesity

    OpenAIRE

    Sun, Xulong; Li, Pengzhou; Yang, Xiangwu; Li, Weizheng; Qiu, Xianjie; Zhu, Shaihong

    2017-01-01

    Abstract Obesity has become a major global health problem, epitomized by excess accumulation of body fat resulting from an imbalance between energy intake and expenditure. The treatments for obesity range from modified nutrition and additional physical activity, to drugs or surgery. But the curative effect of each method seems to vary between individuals. With progress in the genetics and epigenetics of obesity, personalization of the clinical management of obesity may be at our doorstep. Thi...

  19. genetics, epigenetics and the story of mutual antagonisms

    Indian Academy of Sciences (India)

    Recent years have seen a rapid growth in mouse genetics resources that support research into fundamental mechanisms in organogenesis, including those controlling mammalian sex determinations. Numerous mouse mutants have shed light on molecular pathways of cell fate specification during gonadogenesis and the ...

  20. The Contribution of Epigenetics to Understanding Genetic Factors in Autism

    Science.gov (United States)

    Hall, Layla; Kelley, Elizabeth

    2014-01-01

    Autism spectrum disorder is a grouping of neurodevelopmental disorders characterized by deficits in social communication and language, as well as by repetitive and stereotyped behaviors. While the environment is believed to play a role in the development of autism spectrum disorder, there is now strong evidence for a genetic link to autism.…

  1. Genetic and epigenetic variants influencing the development of nonalcoholic fatty liver disease.

    Science.gov (United States)

    Li, Yu-Yuan

    2012-12-07

    Nonalcoholic fatty liver disease (NAFLD) is common worldwide. The importance of genetic and epigenetic changes in etiology and pathogenesis of NAFLD has been increasingly recognized. However, the exact mechanism is largely unknown. A large number of single nucleotide polymorphisms (SNPs) related to NAFLD has been documented by candidate gene studies (CGSs). Among these genes, peroxisome proliferatoractivated receptor-γ, adiponectin, leptin and tumor necrosis factor-α were frequently reported. Since the introduction of genome-wide association studies (GWASs), there have been significant advances in our understanding of genomic variations of NAFLD. Patatin-like phospholipase domain containing family member A3 (PNPLA3, SNP rs738409, encoding I148M), also termed adiponutrin, has caught most attention. The evidence that PNPLA3 is associated with increased hepatic fat levels and hepatic inflammation has been validated by a series of studies. Epigenetic modification refers to phenotypic changes caused by an adaptive mechanism unrelated to alteration of primary DNA sequences. Epigenetic regulation mainly includes microRNAs (miRs), DNA methylation, histone modifications and ubiquitination, among which miRs are studied most extensively. miRs are small natural single stranded RNA molecules regulating mRNA degradation or translation inhibition, subsequently altering protein expression of target genes. The miR-122, a highly abundant miR accounting for nearly 70% of all miRs in the liver, is significantly under-expressed in NAFLD subjects. Inhibition of miR-122 with an antisense oligonucleotide results in decreased mRNA expression of lipogenic genes and improvement of liver steatosis. The investigation into epigenetic involvement in NAFLD pathogenesis is just at the beginning and needs to be refined. This review summarizes the roles of genetics and epigenetics in the development of NAFLD. The progress made in this field may provide novel diagnostic biomarkers and therapeutic

  2. Cisplatin resistance: a cellular self-defense mechanism resulting from multiple epigenetic and genetic changes.

    Science.gov (United States)

    Shen, Ding-Wu; Pouliot, Lynn M; Hall, Matthew D; Gottesman, Michael M

    2012-07-01

    Cisplatin is one of the most effective broad-spectrum anticancer drugs. Its effectiveness seems to be due to the unique properties of cisplatin, which enters cells via multiple pathways and forms multiple different DNA-platinum adducts while initiating a cellular self-defense system by activating or silencing a variety of different genes, resulting in dramatic epigenetic and/or genetic alternations. As a result, the development of cisplatin resistance in human cancer cells in vivo and in vitro by necessity stems from bewilderingly complex genetic and epigenetic changes in gene expression and alterations in protein localization. Extensive published evidence has demonstrated that pleiotropic alterations are frequently detected during development of resistance to this toxic metal compound. Changes occur in almost every mechanism supporting cell survival, including cell growth-promoting pathways, apoptosis, developmental pathways, DNA damage repair, and endocytosis. In general, dozens of genes are affected in cisplatin-resistant cells, including pathways involved in copper metabolism as well as transcription pathways that alter the cytoskeleton, change cell surface presentation of proteins, and regulate epithelial-to-mesenchymal transition. Decreased accumulation is one of the most common features resulting in cisplatin resistance. This seems to be a consequence of numerous epigenetic and genetic changes leading to the loss of cell-surface binding sites and/or transporters for cisplatin, and decreased fluid phase endocytosis.

  3. Inverse relationship between genetic diversity and epigenetic complexity

    OpenAIRE

    Shi Huang

    2008-01-01

    Early studies of molecular evolution revealed a correlation between genetic distance and time of species divergence. This observation provoked the molecular clock hypothesis and in turn the ‘Neutral Theory’, which however remains an incomplete explanation since it predicts a constant mutation rate per generation whereas empirical evidence suggests a constant rate per year. Data inconsistent with the molecular clock hypothesis have steadily accumulated in recent years that show...

  4. Comparative epigenetic and genetic spatial structure of the perennial herb Helleborus foetidus: Isolation by environment, isolation by distance, and functional trait divergence.

    Science.gov (United States)

    Herrera, Carlos M; Medrano, Mónica; Bazaga, Pilar

    2017-08-16

    Epigenetic variation can play a role in local adaptation; thus, there should be associations among epigenetic variation, environmental variation, and functional trait variation across populations. This study examines these relationships in the perennial herb Helleborus foetidus (Ranunculaceae). Plants from 10 subpopulations were characterized genetically (AFLP, SSR markers), epigenetically (MSAP markers), and phenotypically (20 functional traits). Habitats were characterized using six environmental variables. Isolation-by-distance (IBD) and isolation-by-environment (IBE) patterns of genetic and epigenetic divergence were assessed, as was the comparative explanatory value of geographical and environmental distance as predictors of epigenetic, genetic, and functional differentiation. Subpopulations were differentiated genetically, epigenetically, and phenotypically. Genetic differentiation was best explained by geographical distance, while epigenetic differentiation was best explained by environmental distance. Divergence in functional traits was correlated with environmental and epigenetic distances, but not with geographical and genetic distances. Results are compatible with the hypothesis that epigenetic IBE and functional divergence reflected responses to environmental variation. Spatial analyses simultaneously considering epigenetic, genetic, phenotypic and environmental information provide a useful tool to evaluate the role of environmental features as drivers of natural epigenetic variation between populations. © 2017 Botanical Society of America.

  5. Epigenetic regulation in obesity.

    Science.gov (United States)

    Drummond, Elaine M; Gibney, Eileen R

    2013-07-01

    Research suggests that 65% of variation in obesity is genetic. However, much of the known genetic associations have little known function and their effect size small, thus the gene-environment interaction, including epigenetic influences on gene expression, is suggested to be an important factor in the susceptibilty to obesity. This review will explore the potential of epigenetic markers to influence expression of genes associated with obesity. Epigenetic changes in utero are known to have direct implications on the phenotype of the offspring. More recently work has focused on how such epigenetic changes continue to regulate risk of obesity from infancy through to adulthood. Work has shown that, for example, hypomethylation of the MC4 gene causes an increase in expression, and has a direct impact on appetite and intake, and thus influences risk of obesity. Similar influences are also seen in other aspects of obesity including inflammation and adiposity. Maternal diet during foetal development has many epigenetic implications, which affect the offspring's risk factors for obesity during childhood and adulthood, and even in subsequent generations. Genes associated with risk of obesity, are susceptible to epigenetic mutations, which have subsequent effects on disease mechanisms, such as appetite and impaired glucose and insulin tolerance.

  6. Origins of magic: review of genetic and epigenetic effects.

    Science.gov (United States)

    Ramagopalan, Sreeram V; Knight, Marian; Ebers, George C; Knight, Julian C

    2007-12-22

    To assess the evidence for a genetic basis to magic. Literature review. Harry Potter novels of J K Rowling. Muggles, witches, wizards, and squibs. Limited. Family and twin studies, magical ability, and specific magical skills. Magic shows strong evidence of heritability, with familial aggregation and concordance in twins. Evidence suggests magical ability to be a quantitative trait. Specific magical skills, notably being able to speak to snakes, predict the future, and change hair colour, all seem heritable. A multilocus model with a dominant gene for magic might exist, controlled epistatically by one or more loci, possibly recessive in nature. Magical enhancers regulating gene expressionmay be involved, combined with mutations at specific genes implicated in speech and hair colour such as FOXP2 and MCR1.

  7. Epigenetics and genetics in endometrial cancer: new carcinogenic mechanisms and relationship with clinical practice.

    Science.gov (United States)

    Banno, Kouji; Kisu, Iori; Yanokura, Megumi; Masuda, Kenta; Ueki, Arisa; Kobayashi, Yusuke; Susumu, Nobuyuki; Aoki, Daisuke

    2012-04-01

    Endometrial cancer is the seventh most common cancer worldwide among females. An increased incidence and a younger age of patients are also predicted to occur, and therefore elucidation of the pathological mechanisms is important. However, several aspects of the mechanism of carcinogenesis in the endometrium remain unclear. Associations with genetic mutations of cancer-related genes have been shown, but these do not provide a complete explanation. Therefore, epigenetic mechanisms have been examined. Silencing of genes by DNA hypermethylation, hereditary epimutation of DNA mismatch repair genes and regulation of gene expression by miRNAs may underlie carcinogenesis in endometrial cancer. New therapies include targeting epigenetic changes using histone deacetylase inhibitors. Some cases of endometrial cancer may also be hereditary. Thus, patients with Lynch syndrome which is a hereditary disease, have a higher risk for developing endometrial cancer than the general population. Identification of such disease-related genes may contribute to early detection and prevention of endometrial cancer.

  8. Genetic Variants in Epigenetic Pathways and Risks of Multiple Cancers in the GAME-ON Consortium.

    Science.gov (United States)

    Toth, Reka; Scherer, Dominique; Kelemen, Linda E; Risch, Angela; Hazra, Aditi; Balavarca, Yesilda; Issa, Jean-Pierre J; Moreno, Victor; Eeles, Rosalind A; Ogino, Shuji; Wu, Xifeng; Ye, Yuanqing; Hung, Rayjean J; Goode, Ellen L; Ulrich, Cornelia M

    2017-06-01

    Background: Epigenetic disturbances are crucial in cancer initiation, potentially with pleiotropic effects, and may be influenced by the genetic background. Methods: In a subsets (ASSET) meta-analytic approach, we investigated associations of genetic variants related to epigenetic mechanisms with risks of breast, lung, colorectal, ovarian and prostate carcinomas using 51,724 cases and 52,001 controls. False discovery rate-corrected P values (q values cancer type. For example, variants in BABAM1 were confirmed as a susceptibility locus for squamous cell lung, overall breast, estrogen receptor (ER)-negative breast, and overall prostate, and overall serous ovarian cancer; the most significant variant was rs4808076 [OR = 1.14; 95% confidence interval (CI) = 1.10-1.19; q = 6.87 × 10 -5 ]. DPF1 rs12611084 was inversely associated with ER-negative breast, endometrioid ovarian, and overall and aggressive prostate cancer risk (OR = 0.93; 95% CI = 0.91-0.96; q = 0.005). Variants in L3MBTL3 were associated with colorectal, overall breast, ER-negative breast, clear cell ovarian, and overall and aggressive prostate cancer risk (e.g., rs9388766: OR = 1.06; 95% CI = 1.03-1.08; q = 0.02). Variants in TET2 were significantly associated with overall breast, overall prostate, overall ovarian, and endometrioid ovarian cancer risk, with rs62331150 showing bidirectional effects. Analyses of subpathways did not reveal gene subsets that contributed disproportionately to susceptibility. Conclusions: Functional and correlative studies are now needed to elucidate the potential links between germline genotype, epigenetic function, and cancer etiology. Impact: This approach provides novel insight into possible pleiotropic effects of genes involved in epigenetic processes. Cancer Epidemiol Biomarkers Prev; 26(6); 816-25. ©2017 AACR . ©2017 American Association for Cancer Research.

  9. Epigenetic cell response to an influence of ionizing radiation

    International Nuclear Information System (INIS)

    Mikheev, A.N.; Gushcha, N.I.; Malinovskij, Yu.Yu.

    1999-01-01

    Importance of radiation modification of epigenetic activity in the general mechanism of radiobiological reactions is proved. Inheritable epigenetic changes induced by irradiation are one of the basic reasons of formation of the remote radiation pathology. It is noted that epigenetic inheritable changes of cells have the determined character distinguishing them mutation changes, being individual and not directed. It is underlined the ability of ionizing radiation to modify level of spontaneous genetic instability inherited in a number of cell generations on epigenetic mechanism [ru

  10. Assessment of genetic and epigenetic variation in hop plants regenerated from sequential subcultures of organogenic calli.

    Science.gov (United States)

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

    2006-10-01

    Organogenic calli induced from internodal segments were subcultured three times. Regenerated plants obtained from each subculture were analysed by molecular methods. No major genetic rearrangements were detected in the callus-derived plants since none of the amplified fragment-length polymorphism (AFLP) loci were found to be polymorphic. However, epigenetic changes due to a demethylation process were detected by methylation-sensitive amplified polymorphism (MSAP) technique. The results allowed inference of the possible relationship among the plants derived from different calli subcultures and the in vitro control. The plants recovered from the first and second callus subcultures clustered with the in vitro control pools in the phenogram while the regenerants from the third callus subculture showed the highest genetic distance with the controls. This is the first study reporting data about the genetic stability of callus-derived Humulus lupulus L. plants.

  11. Genetic and Epigenetic Regulation of Human Cardiac Reprogramming and Differentiation in Regenerative Medicine.

    Science.gov (United States)

    Burridge, Paul W; Sharma, Arun; Wu, Joseph C

    2015-01-01

    Regeneration or replacement of lost cardiomyocytes within the heart has the potential to revolutionize cardiovascular medicine. Numerous methodologies have been used to achieve this aim, including the engraftment of bone marrow- and heart-derived cells as well as the identification of modulators of adult cardiomyocyte proliferation. Recently, the conversion of human somatic cells into induced pluripotent stem cells and induced cardiomyocyte-like cells has transformed potential approaches toward this goal, and the engraftment of cardiac progenitors derived from human embryonic stem cells into patients is now feasible. Here we review recent advances in our understanding of the genetic and epigenetic control of human cardiogenesis, cardiac differentiation, and the induced reprogramming of somatic cells to cardiomyocytes. We also cover genetic programs for inducing the proliferation of endogenous cardiomyocytes and discuss the genetic state of cells used in cardiac regenerative medicine.

  12. Hypothesis: Genetic and epigenetic risk factors interact to modulate vulnerability and resilience to FASD

    Directory of Open Access Journals (Sweden)

    Elif eTunc-Ozcan

    2014-08-01

    Full Text Available Fetal alcohol spectrum disorder (FASD presents a collection of symptoms representing physiological and behavioral phenotypes caused by maternal alcohol consumption. Symptom severity is modified by genetic differences in fetal susceptibility and resistance as well as maternal genetic factors such as maternal alcohol sensitivity. Animal models demonstrate that both maternal and paternal genetics contribute to the variation in the fetus’ vulnerability to alcohol exposure. Maternal and paternal genetics define the variations in these phenotypes even without the effect of alcohol in utero, as most of these traits are polygenic, non-Mendelian, in their inheritance. In addition, the epigenetic alterations that instigate the alcohol induced neurodevelopmental deficits can interact with the polygenic inheritance of respective traits. Here, based on specific examples, we present the hypothesis that the principles of non-Mendelian inheritance, or ‘exceptions’ to Mendelian genetics, can be the driving force behind the severity of the prenatal alcohol-exposed individual’s symptomology. One such exception is when maternal alleles lead to an altered intrauterine hormonal environment and, therefore, produce variations in the long-term consequences on the development of the alcohol-exposed fetus. Another exception is when epigenetic regulation of allele-specific gene expression generates disequilibrium between the maternal versus paternal genetic contributions, and thereby, modifies the effect of prenatal alcohol exposure on the fetus. We propose that these situations in which one parent has an exaggerated influence over the offspring’s vulnerability to prenatal alcohol are major contributing mechanisms responsible for the variations in the symptomology of FASD in the exposed generation and beyond.

  13. Neurofibromatosis-Noonan Syndrome: A Possible Paradigm of the Combination of Genetic and Epigenetic Factors.

    Science.gov (United States)

    Yapijakis, Christos; Pachis, Nikos; Voumvourakis, Costas

    2017-01-01

    Neurofibromatosis-Noonan syndrome (NFNS) is a clinical entity possessing traits of autosomal dominant disorders neurofibromatosis type 1 (NF1) and Noonan syndrome (NS). Germline mutations that disrupt the RAS/MAPK pathway are involved in the pathogenesis of both NS and NF1. In light of a studied Greek family, a new theory for etiological pathogenesis of NFNS is suggested. The NFNS phenotype may be the final result of a combination of a genetic factor (a mutation in the NF1 gene) and an environmental factor with the epigenetic effects of muscle hypotonia (such as hydantoin in the reported Greek family), causing hypoplasia of the face and micrognathia.

  14. Untangling individual variation in natural populations: ecological, genetic and epigenetic correlates of long-term inequality in herbivory.

    Science.gov (United States)

    Herrera, C M; Bazaga, P

    2011-04-01

    Individual variation in ecologically important features of organisms is a crucial element in ecology and evolution, yet disentangling its underlying causes is difficult in natural populations. We applied a genomic scan approach using amplified fragment length polymorphism (AFLP) markers to quantify the genetic basis of long-term individual differences in herbivory by mammals at a wild population of the violet Viola cazorlensis monitored for two decades. In addition, methylation-sensitive amplified polymorphism (MSAP) analyses were used to investigate the association between browsing damage and epigenetic characteristics of individuals, an aspect that has been not previously explored for any wild plant. Structural equation modelling was used to identify likely causal structures linking genotypes, epigenotypes and herbivory. Individuals of V. cazorlensis differed widely in the incidence of browsing mammals over the 20-year study period. Six AFLP markers (1.6% of total) were significantly related to herbivory, accounting altogether for 44% of population-wide variance in herbivory levels. MSAP analyses revealed considerable epigenetic variation among individuals, and differential browsing damage was significantly related to variation in multilocus epigenotypes. In addition, variation across plants in epigenetic characteristics was related to variation in several herbivory-related AFLP markers. Statistical comparison of alternative causal models suggested that individual differences in herbivory are the outcome of a complex causal structure where genotypes and epigenotypes are interconnected and have direct and indirect effects on herbivory. Insofar as methylation states of MSAP markers influential on herbivory are transgenerationally heritable, herbivore-driven evolutionary changes at the study population will involve correlated changes in genotypic and epigenotypic distributions. © 2011 Blackwell Publishing Ltd.

  15. Recent progress in genetics, epigenetics and metagenomics unveils the pathophysiology of human obesity.

    Science.gov (United States)

    Pigeyre, Marie; Yazdi, Fereshteh T; Kaur, Yuvreet; Meyre, David

    2016-06-01

    In high-, middle- and low-income countries, the rising prevalence of obesity is the underlying cause of numerous health complications and increased mortality. Being a complex and heritable disorder, obesity results from the interplay between genetic susceptibility, epigenetics, metagenomics and the environment. Attempts at understanding the genetic basis of obesity have identified numerous genes associated with syndromic monogenic, non-syndromic monogenic, oligogenic and polygenic obesity. The genetics of leanness are also considered relevant as it mirrors some of obesity's aetiologies. In this report, we summarize ten genetically elucidated obesity syndromes, some of which are involved in ciliary functioning. We comprehensively review 11 monogenic obesity genes identified to date and their role in energy maintenance as part of the leptin-melanocortin pathway. With the emergence of genome-wide association studies over the last decade, 227 genetic variants involved in different biological pathways (central nervous system, food sensing and digestion, adipocyte differentiation, insulin signalling, lipid metabolism, muscle and liver biology, gut microbiota) have been associated with polygenic obesity. Advances in obligatory and facilitated epigenetic variation, and gene-environment interaction studies have partly accounted for the missing heritability of obesity and provided additional insight into its aetiology. The role of gut microbiota in obesity pathophysiology, as well as the 12 genes associated with lipodystrophies is discussed. Furthermore, in an attempt to improve future studies and merge the gap between research and clinical practice, we provide suggestions on how high-throughput '-omic' data can be integrated in order to get closer to the new age of personalized medicine. © 2016 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  16. Genetic, epigenetic, and HPLC fingerprint differentiation between natural and ex situ populations of Rhodiola sachalinensis from Changbai Mountain, China.

    Directory of Open Access Journals (Sweden)

    Wei Zhao

    Full Text Available Rhodiola sachalinensis is an endangered species with important medicinal value. We used inter-simple sequence repeat (ISSR and methylation-sensitive amplified polymorphism (MSAP markers to analyze genetic and epigenetic differentiation in different populations of R. sachalinensis, including three natural populations and an ex situ population. Chromatographic fingerprint was used to reveal HPLC fingerprint differentiation. According to our results, the ex situ population of R. sachalinensis has higher level genetic diversity and greater HPLC fingerprint variation than natural populations, but shows lower epigenetic diversity. Most genetic variation (54.88% was found to be distributed within populations, and epigenetic variation was primarily distributed among populations (63.87%. UPGMA cluster analysis of ISSR and MSAP data showed identical results, with individuals from each given population grouping together. The results of UPGMA cluster analysis of HPLC fingerprint patterns was significantly different from results obtained from ISSR and MSAP data. Correlation analysis revealed close relationships among altitude, genetic structure, epigenetic structure, and HPLC fingerprint patterns (R2 = 0.98 for genetic and epigenetic distance; R2 = 0.90 for DNA methylation level and altitude; R2 = -0.95 for HPLC fingerprint and altitude. Taken together, our results indicate that ex situ population of R. sachalinensis show significantly different genetic and epigenetic population structures and HPLC fingerprint patterns. Along with other potential explanations, these findings suggest that the ex situ environmental factors caused by different altitude play an important role in keeping hereditary characteristic of R. sachalinensis.

  17. Genetic, epigenetic, and HPLC fingerprint differentiation between natural and ex situ populations of Rhodiola sachalinensis from Changbai Mountain, China.

    Science.gov (United States)

    Zhao, Wei; Shi, Xiaozheng; Li, Jiangnan; Guo, Wei; Liu, Chengbai; Chen, Xia

    2014-01-01

    Rhodiola sachalinensis is an endangered species with important medicinal value. We used inter-simple sequence repeat (ISSR) and methylation-sensitive amplified polymorphism (MSAP) markers to analyze genetic and epigenetic differentiation in different populations of R. sachalinensis, including three natural populations and an ex situ population. Chromatographic fingerprint was used to reveal HPLC fingerprint differentiation. According to our results, the ex situ population of R. sachalinensis has higher level genetic diversity and greater HPLC fingerprint variation than natural populations, but shows lower epigenetic diversity. Most genetic variation (54.88%) was found to be distributed within populations, and epigenetic variation was primarily distributed among populations (63.87%). UPGMA cluster analysis of ISSR and MSAP data showed identical results, with individuals from each given population grouping together. The results of UPGMA cluster analysis of HPLC fingerprint patterns was significantly different from results obtained from ISSR and MSAP data. Correlation analysis revealed close relationships among altitude, genetic structure, epigenetic structure, and HPLC fingerprint patterns (R2 = 0.98 for genetic and epigenetic distance; R2 = 0.90 for DNA methylation level and altitude; R2 = -0.95 for HPLC fingerprint and altitude). Taken together, our results indicate that ex situ population of R. sachalinensis show significantly different genetic and epigenetic population structures and HPLC fingerprint patterns. Along with other potential explanations, these findings suggest that the ex situ environmental factors caused by different altitude play an important role in keeping hereditary characteristic of R. sachalinensis.

  18. Epigenetic and genetic factors in the cellular response to radiations and DNA-damaging chemicals

    International Nuclear Information System (INIS)

    Williams, J.R.; D'Arpa, P.

    1981-01-01

    DNA-damaging agents are widely used as therapeutic tools for a variety of disease states. Many such agents are considered to produce detrimental side effects. Thus, it is important to evaluate both therapeutic efficacy and potential risk. DNA-damaging agents can be so evaluated by comparison to agents whose therapeutic benefit and potential hazards are better known. We propose a framework for such comparison, demonstrating that a simple transformation of cytotoxicity-dose response patterns permits a facile comparison of variation between cells exposed to a single DNA-damaging agent or to different cytotoxic agents. Further, by transforming data from experiments which compare responses of 2 cell populations to an effects ratio, different patterns for the changes in cytotoxicity produced by epigenetic and genetic factors were compared. Using these transformations, we found that there is a wide variation (a factor of 4) between laboratories for a single agent (UVC) and only a slightly larger variation (factor of 6) between normal cell response for different types of DNA-damaging agents (x-ray, UVC, alkylating agents, crosslinking agents). Epigenetic factors such as repair and recovery appear to be a factor only at higher dose levels. Comparison in the cytotoxic effect of a spectrum of DNA-damaging agents in xeroderma pigmentosum, ataxia telangiectasia, and Fanconi's anemia cells indicates significantly different patterns, implying that the effect, and perhaps the nature, of these genetic conditions are quite different

  19. Genetic Mutations and Epigenetic Modifications: Driving Cancer and Informing Precision Medicine

    Science.gov (United States)

    Coyle, Krysta Mila; Boudreau, Jeanette E.

    2017-01-01

    Cancer treatment is undergoing a significant revolution from “one-size-fits-all” cytotoxic therapies to tailored approaches that precisely target molecular alterations. Precision strategies for drug development and patient stratification, based on the molecular features of tumors, are the next logical step in a long history of approaches to cancer therapy. In this review, we discuss the history of cancer treatment from generic natural extracts and radical surgical procedures to site-specific and combinatorial treatment regimens, which have incrementally improved patient outcomes. We discuss the related contributions of genetics and epigenetics to cancer progression and the response to targeted therapies and identify challenges and opportunities for the success of precision medicine. The identification of patients who will benefit from targeted therapies is more complex than simply identifying patients whose tumors harbour the targeted aberration, and intratumoral heterogeneity makes it difficult to determine if a precision therapy is successful during treatment. This heterogeneity enables tumors to develop resistance to targeted approaches; therefore, the rational combination of therapeutic agents will limit the threat of acquired resistance to therapeutic success. By incorporating the view of malignant transformation modulated by networks of genetic and epigenetic interactions, molecular strategies will enable precision medicine for effective treatment across cancer subtypes. PMID:28685150

  20. Rapid Genetic and Epigenetic Alterations under Intergeneric Genomic Shock in Newly Synthesized Chrysanthemum morifolium × Leucanthemum paludosum Hybrids (Asteraceae)

    Science.gov (United States)

    Wang, Haibin; Jiang, Jiafu; Chen, Sumei; Qi, Xiangyu; Fang, Weimin; Guan, Zhiyong; Teng, Nianjun; Liao, Yuan; Chen, Fadi

    2014-01-01

    The Asteraceae family is at the forefront of the evolution due to frequent hybridization. Hybridization is associated with the induction of widespread genetic and epigenetic changes and has played an important role in the evolution of many plant taxa. We attempted the intergeneric cross Chrysanthemum morifolium × Leucanthemum paludosum. To obtain the success in cross, we have to turn to ovule rescue. DNA profiling of the amphihaploid and amphidiploid was investigated using amplified fragment length polymorphism, sequence-related amplified polymorphism, start codon targeted polymorphism, and methylation-sensitive amplification polymorphism (MSAP). Hybridization induced rapid changes at the genetic and the epigenetic levels. The genetic changes mainly involved loss of parental fragments and gaining of novel fragments, and some eliminated sequences possibly from the noncoding region of L. paludosum. The MSAP analysis indicated that the level of DNA methylation was lower in the amphiploid (∼45%) than in the parental lines (51.5–50.6%), whereas it increased after amphidiploid formation. Events associated with intergeneric genomic shock were a feature of C. morifolium × L. paludosum hybrid, given that the genetic relationship between the parental species is relatively distant. Our results provide genetic and epigenetic evidence for understanding genomic shock in wide crosses between species in Asteraceae and suggest a need to expand our current evolutionary framework to encompass a genetic/epigenetic dimension when seeking to understand wide crosses. PMID:24407856

  1. Rapid genetic and epigenetic alterations under intergeneric genomic shock in newly synthesized Chrysanthemum morifolium x Leucanthemum paludosum hybrids (Asteraceae).

    Science.gov (United States)

    Wang, Haibin; Jiang, Jiafu; Chen, Sumei; Qi, Xiangyu; Fang, Weimin; Guan, Zhiyong; Teng, Nianjun; Liao, Yuan; Chen, Fadi

    2014-01-01

    The Asteraceae family is at the forefront of the evolution due to frequent hybridization. Hybridization is associated with the induction of widespread genetic and epigenetic changes and has played an important role in the evolution of many plant taxa. We attempted the intergeneric cross Chrysanthemum morifolium × Leucanthemum paludosum. To obtain the success in cross, we have to turn to ovule rescue. DNA profiling of the amphihaploid and amphidiploid was investigated using amplified fragment length polymorphism, sequence-related amplified polymorphism, start codon targeted polymorphism, and methylation-sensitive amplification polymorphism (MSAP). Hybridization induced rapid changes at the genetic and the epigenetic levels. The genetic changes mainly involved loss of parental fragments and gaining of novel fragments, and some eliminated sequences possibly from the noncoding region of L. paludosum. The MSAP analysis indicated that the level of DNA methylation was lower in the amphiploid (∼45%) than in the parental lines (51.5-50.6%), whereas it increased after amphidiploid formation. Events associated with intergeneric genomic shock were a feature of C. morifolium × L. paludosum hybrid, given that the genetic relationship between the parental species is relatively distant. Our results provide genetic and epigenetic evidence for understanding genomic shock in wide crosses between species in Asteraceae and suggest a need to expand our current evolutionary framework to encompass a genetic/epigenetic dimension when seeking to understand wide crosses.

  2. Genetic and epigenetic features in radiation sensitivity. Part I: Cell signalling in radiation response

    International Nuclear Information System (INIS)

    Bourguignon, Michel H.; Gisone, Pablo A.; Perez, Maria R.; Michelin, Severino; Dubner, Diana; Giorgio, Marina di; Carosella, Edgardo D.

    2005-01-01

    Recent progress especially in the field of gene identification and expression has attracted greater attention to genetic and epigenetic susceptibility to cancer, possibly enhanced by ionising radiation. It has been proposed that the occurrence and severity of the adverse reactions to radiation therapy are also influenced by such genetic susceptibility. This issue is especially important for radiation therapists since hypersensitive patients may suffer from adverse effects in normal tissues following standard radiation therapy, while normally sensitive patients could receive higher doses of radiation offering a better likelihood of cure for malignant tumours. This paper, the first of two parts, reviews the main mechanisms involved in cell response to ionising radiation. DNA repair machinery and cell signalling pathways are considered and their role in radiosensitivity is analysed. The implication of non-targeted and delayed effects in radiosensitivity is also discussed. (orig.)

  3. Immediate Genetic and Epigenetic Changes in F1 Hybrids Parented by Species with Divergent Genomes in the Rice Genus (Oryza.

    Directory of Open Access Journals (Sweden)

    Ying Wu

    Full Text Available Inter-specific hybridization occurs frequently in higher plants, and represents a driving force of evolution and speciation. Inter-specific hybridization often induces genetic and epigenetic instabilities in the resultant homoploid hybrids or allopolyploids, a phenomenon known as genome shock. Although genetic and epigenetic consequences of hybridizations between rice subspecies (e.g., japonica and indica and closely related species sharing the same AA genome have been extensively investigated, those of inter-specific hybridizations between more remote species with different genomes in the rice genus, Oryza, remain largely unknown.We investigated the immediate chromosomal and molecular genetic/epigenetic instability of three triploid F1 hybrids produced by inter-specific crossing between species with divergent genomes of Oryza by genomic in situ hybridization (GISH and molecular marker analysis. Transcriptional and transpositional activity of several transposable elements (TEs and methylation stability of their flanking regions were also assessed. We made the following principle findings: (i all three triploid hybrids are stable in both chromosome number and gross structure; (ii stochastic changes in both DNA sequence and methylation occurred in individual plants of all three triploid hybrids, but in general methylation changes occurred at lower frequencies than genetic changes; (iii alteration in DNA methylation occurred to a greater extent in genomic loci flanking potentially active TEs than in randomly sampled loci; (iv transcriptional activation of several TEs commonly occurred in all three hybrids but transpositional events were detected in a genetic context-dependent manner.Artificially constructed inter-specific hybrids of remotely related species with divergent genomes in genus Oryza are chromosomally stable but show immediate and highly stochastic genetic and epigenetic instabilities at the molecular level. These novel hybrids might

  4. Tissue culture-induced genetic and epigenetic alterations in rice pure-lines, F1 hybrids and polyploids.

    Science.gov (United States)

    Wang, Xiaoran; Wu, Rui; Lin, Xiuyun; Bai, Yan; Song, Congdi; Yu, Xiaoming; Xu, Chunming; Zhao, Na; Dong, Yuzhu; Liu, Bao

    2013-05-05

    Genetic and epigenetic alterations can be invoked by plant tissue culture, which may result in heritable changes in phenotypes, a phenomenon collectively termed somaclonal variation. Although extensive studies have been conducted on the molecular nature and spectrum of tissue culture-induced genomic alterations, the issue of whether and to what extent distinct plant genotypes, e.g., pure-lines, hybrids and polyploids, may respond differentially to the tissue culture condition remains poorly understood. We investigated tissue culture-induced genetic and epigenetic alterations in a set of rice genotypes including two pure-lines (different subspecies), a pair of reciprocal F1 hybrids parented by the two pure-lines, and a pair of reciprocal tetraploids resulted from the hybrids. Using two molecular markers, amplified fragment length polymorphism (AFLP) and methylation-sensitive amplified polymorphism (MSAP), both genetic and DNA methylation alterations were detected in calli and regenerants from all six genotypes, but genetic alteration is more prominent than epigenetic alteration. While significant genotypic difference was observed in frequencies of both types of alterations, only genetic alteration showed distinctive features among the three types of genomes, with one hybrid (N/9) being exceptionally labile. Surprisingly, difference in genetic alteration frequencies between the pair of reciprocal F1 hybrids is much greater than that between the two pure-line subspecies. Difference also exists in the pair of reciprocal tetraploids, but is to a less extent than that between the hybrids. The steady-state transcript abundance of genes involved in DNA repair and DNA methylation was significantly altered in both calli and regenerants, and some of which were correlated with the genetic and/or epigenetic alterations. Our results, based on molecular marker analysis of ca. 1,000 genomic loci, document that genetic alteration is the major cause of somaclonal variation in rice

  5. Epigenetic Alterations in Alzheimer’s Disease

    Science.gov (United States)

    Sanchez-Mut, Jose V.; Gräff, Johannes

    2015-01-01

    Alzheimer’s disease (AD) is the major cause of dementia in Western societies. It progresses asymptomatically during decades before being belatedly diagnosed when therapeutic strategies have become unviable. Although several genetic alterations have been associated with AD, the vast majority of AD cases do not show strong genetic underpinnings and are thus considered a consequence of non-genetic factors. Epigenetic mechanisms allow for the integration of long-lasting non-genetic inputs on specific genetic backgrounds, and recently, a growing number of epigenetic alterations in AD have been described. For instance, an accumulation of dysregulated epigenetic mechanisms in aging, the predominant risk factor of AD, might facilitate the onset of the disease. Likewise, mutations in several enzymes of the epigenetic machinery have been associated with neurodegenerative processes that are altered in AD such as impaired learning and memory formation. Genome-wide and locus-specific epigenetic alterations have also been reported, and several epigenetically dysregulated genes validated by independent groups. From these studies, a picture emerges of AD as being associated with DNA hypermethylation and histone deacetylation, suggesting a general repressed chromatin state and epigenetically reduced plasticity in AD. Here we review these recent findings and discuss several technical and methodological considerations that are imperative for their correct interpretation. We also pay particular focus on potential implementations and theoretical frameworks that we expect will help to better direct future studies aimed to unravel the epigenetic participation in AD. PMID:26734709

  6. Early-life nutrition modulates the epigenetic state of specific rDNA genetic variants in mice.

    Science.gov (United States)

    Holland, Michelle L; Lowe, Robert; Caton, Paul W; Gemma, Carolina; Carbajosa, Guillermo; Danson, Amy F; Carpenter, Asha A M; Loche, Elena; Ozanne, Susan E; Rakyan, Vardhman K

    2016-07-29

    A suboptimal early-life environment, due to poor nutrition or stress during pregnancy, can influence lifelong phenotypes in the progeny. Epigenetic factors are thought to be key mediators of these effects. We show that protein restriction in mice from conception until weaning induces a linear correlation between growth restriction and DNA methylation at ribosomal DNA (rDNA). This epigenetic response remains into adulthood and is restricted to rDNA copies associated with a specific genetic variant within the promoter. Related effects are also found in models of maternal high-fat or obesogenic diets. Our work identifies environmentally induced epigenetic dynamics that are dependent on underlying genetic variation and establishes rDNA as a genomic target of nutritional insults. Copyright © 2016, American Association for the Advancement of Science.

  7. Assessment of genetic and epigenetic variation during long-term Taxus cell culture.

    Science.gov (United States)

    Fu, Chunhua; Li, Liqin; Wu, Wenjuan; Li, Maoteng; Yu, Xiaoqing; Yu, Longjiang

    2012-07-01

    Gradual loss of secondary metabolite production is a common obstacle in the development of a large-scale plant cell production system. In this study, cell morphology, paclitaxel (Taxol®) biosynthetic ability, and genetic and epigenetic variations in the long-term culture of Taxus media cv Hicksii cells were assessed over a 5-year period to evaluate the mechanisms of the loss of secondary metabolites biosynthesis capacity in Taxus cell. The results revealed that morphological variations, gradual loss of paclitaxel yield and decreased transcriptional level of paclitaxel biosynthesis key genes occurred during long-term subculture. Genetic and epigenetic variations in these cultures were also studied at different times during culture using amplified fragment-length polymorphism (AFLP), methylation-sensitive amplified polymorphism (MSAP), and high-performance liquid chromatography (HPLC) analyses. A total of 32 primer combinations were used in AFLP amplification, and none of the AFLP loci were found to be polymorphic, thus no major genetic rearrangements were detected in any of the tested samples. However, results from both MSAP and HPLC indicated that there was a higher level of DNA methylation in the low-paclitaxel yielding cell line after long-term culture. Based on these results, we proposed that accumulation of paclitaxel in Taxus cell cultures might be regulated by DNA methylation. To our knowledge, this is the first report of increased methylation with the prolongation of culture time in Taxus cell culture. It provides substantial clues for exploring the gradual loss of the taxol biosynthesis capacity of Taxus cell lines during long-term subculture. DNA methylation maybe involved in the regulation of paclitaxel biosynthesis in Taxus cell culture.

  8. Integrated genetic and epigenetic prediction of coronary heart disease in the Framingham Heart Study.

    Directory of Open Access Journals (Sweden)

    Meeshanthini V Dogan

    Full Text Available An improved method for detecting coronary heart disease (CHD could have substantial clinical impact. Building on the idea that systemic effects of CHD risk factors are a conglomeration of genetic and environmental factors, we use machine learning techniques and integrate genetic, epigenetic and phenotype data from the Framingham Heart Study to build and test a Random Forest classification model for symptomatic CHD. Our classifier was trained on n = 1,545 individuals and consisted of four DNA methylation sites, two SNPs, age and gender. The methylation sites and SNPs were selected during the training phase. The final trained model was then tested on n = 142 individuals. The test data comprised of individuals removed based on relatedness to those in the training dataset. This integrated classifier was capable of classifying symptomatic CHD status of those in the test set with an accuracy, sensitivity and specificity of 78%, 0.75 and 0.80, respectively. In contrast, a model using only conventional CHD risk factors as predictors had an accuracy and sensitivity of only 65% and 0.42, respectively, but with a specificity of 0.89 in the test set. Regression analyses of the methylation signatures illustrate our ability to map these signatures to known risk factors in CHD pathogenesis. These results demonstrate the capability of an integrated approach to effectively model symptomatic CHD status. These results also suggest that future studies of biomaterial collected from longitudinally informative cohorts that are specifically characterized for cardiac disease at follow-up could lead to the introduction of sensitive, readily employable integrated genetic-epigenetic algorithms for predicting onset of future symptomatic CHD.

  9. Genetic variation and epigenetic modification of the prodynorphin gene in peripheral blood cells in alcoholism.

    Science.gov (United States)

    D'Addario, Claudio; Shchetynsky, Klementy; Pucci, Mariangela; Cifani, Carlo; Gunnar, Agneta; Vukojević, Vladana; Padyukov, Leonid; Terenius, Lars

    2017-06-02

    Dynorphins are critically involved in the development, maintenance and relapse of alcoholism. Alcohol-induced changes in the prodynorphin gene expression may be influenced by both gene polymorphisms and epigenetic modifications. The present study of human alcoholics aims to evaluate DNA methylation patterns in the prodynorphin gene (PDYN) promoter and to identify single nucleotide polymorphisms (SNPs) associated with alcohol dependence and with altered DNA methylation. Genomic DNA was isolated from peripheral blood cells of alcoholics and healthy controls, and DNA methylation was studied in the PDYN promoter by bisulfite pyrosequencing. In alcoholics, DNA methylation increased in three of the seven CpG sites investigated, as well as in the average of the seven CpG sites. Data stratification showed lower increase in DNA methylation levels in individuals reporting craving and with higher levels of alcohol consumption. Association with alcoholism was observed for rs2235751 and the presence of the minor allele G was associated with reduced DNA methylation at PDYN promoter in females and younger subjects. Genetic and epigenetic factors within PDYN are related to risk for alcoholism, providing further evidence of its involvement on ethanol effects. These results might be of relevance for developing new biomarkers to predict disease trajectories and therapeutic outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Epigenetics and genetic determinism Epigenética e determinismo genético

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    Hernán A. Burbano

    2006-12-01

    Full Text Available This paper posits that the gene-centered viewpoint of the organism (gene-centrism is not enough to explain biological complexity. Organisms are not completely determined by their genomes; rather, living beings can be seen as interpreters or intentional systems. Epigenetics is the framework that allows the avoidance of gene-centrism and permits the emergence of a more holistic standpoint where determination and novelty can coexist, as shown with examples taken from developmental biology and macromolecules folding. In summary, as P. Medawar and J. Medawar wrote: "Genetics proposes; epigenetics disposes."O presente trabalho afirma que a visão geneticista do organismo (genecentrismo não é suficiente para explicar a complexidade biológica. Os organismos não são completamente determinados por seus genomas; ou melhor, os seres vivos podem ser vistos como intérpretes ou sistemas intencionais. A epigenética é o arcabouço que ajuda a evitar o genecentrismo e permite a emergência de uma posição mais holística, em que determinismo e inovação podem coexistir, conforme demonstrado a partir de exemplos retirados da biologia do desenvolvimento e da estrutura das macromoléculas. Em resumo, como P. Medawar e J. Medawar escreveram: "A genética propõe e a epigenética dispõe".

  11. Genetic mechanisms and age-related macular degeneration: common variants, rare variants, copy number variations, epigenetics, and mitochondrial genetics

    Directory of Open Access Journals (Sweden)

    Liu Melissa M

    2012-08-01

    Full Text Available Abstract Age-related macular degeneration (AMD is a complex and multifaceted disease involving contributions from both genetic and environmental influences. Previous work exploring the genetic contributions of AMD has implicated numerous genomic regions and a variety of candidate genes as modulators of AMD susceptibility. Nevertheless, much of this work has revolved around single-nucleotide polymorphisms (SNPs, and it is apparent that a significant portion of the heritability of AMD cannot be explained through these mechanisms. In this review, we consider the role of common variants, rare variants, copy number variations, epigenetics, microRNAs, and mitochondrial genetics in AMD. Copy number variations in regulators of complement activation genes (CFHR1 and CFHR3 and glutathione S transferase genes (GSTM1 and GSTT1 have been associated with AMD, and several additional loci have been identified as regions of potential interest but require further evaluation. MicroRNA dysregulation has been linked to the retinal pigment epithelium degeneration in geographic atrophy, ocular neovascularization, and oxidative stress, all of which are hallmarks in the pathogenesis of AMD. Certain mitochondrial DNA haplogroups and SNPs in mitochondrially encoded NADH dehydrogenase genes have also been associated with AMD. The role of these additional mechanisms remains only partly understood, but the importance of their further investigation is clear to elucidate more completely the genetic basis of AMD.

  12. Genetic and epigenetic control of gene expression by CRISPR–Cas systems

    Science.gov (United States)

    Lo, Albert; Qi, Lei

    2017-01-01

    The discovery and adaption of bacterial clustered regularly interspaced short palindromic repeats (CRISPR)–CRISPR-associated (Cas) systems has revolutionized the way researchers edit genomes. Engineering of catalytically inactivated Cas variants (nuclease-deficient or nuclease-deactivated [dCas]) combined with transcriptional repressors, activators, or epigenetic modifiers enable sequence-specific regulation of gene expression and chromatin state. These CRISPR–Cas-based technologies have contributed to the rapid development of disease models and functional genomics screening approaches, which can facilitate genetic target identification and drug discovery. In this short review, we will cover recent advances of CRISPR–dCas9 systems and their use for transcriptional repression and activation, epigenome editing, and engineered synthetic circuits for complex control of the mammalian genome. PMID:28649363

  13. NEIGHBORHOOD CRIME AND DEPRESSIVE SYMPTOMS AMONG AFRICAN AMERICAN WOMEN: GENETIC MODERATION AND EPIGENETIC MEDIATOIN OF EFFECTS

    Science.gov (United States)

    Lei, Man-Kit; Beach, Steven R. H.; Simons, Ronald L.; Philibert, Robert A.

    2015-01-01

    Introduction Social scientists have long recognized the important role that neighborhood crime can play in stress-related disease, but very little is known about potential biosocial mechanisms that may link the experience of living in high-crime neighborhoods with depression. Objective The current study introduces an integrated model that combines neighborhood, genetic, and epigenetic factors. Methods Hypotheses were tested with a sample of 99 African American women from the Family and Community Health Study (FACHS). Results Allele variants of the serotonin transporter gene (5-HTT) interact with neighborhood crime to predict depressive symptoms in a manner consonant with the differential susceptibility perspective. Furthermore, this association is mediated by DNA methylation of the promoter region of the serotonin transporter gene. Conclusion The findings provide support for an integrated model in which changes in DNA methylation, resulting from neighborhood crime, can result in an increase or decrease in gene activity which, in turn, influences depressive symptoms. PMID:26513121

  14. Neighborhood crime and depressive symptoms among African American women: Genetic moderation and epigenetic mediation of effects.

    Science.gov (United States)

    Lei, Man-Kit; Beach, Steven R H; Simons, Ronald L; Philibert, Robert A

    2015-12-01

    Social scientists have long recognized the important role that neighborhood crime can play in stress-related disease, but very little is known about potential biosocial mechanisms that may link the experience of living in high-crime neighborhoods with depression. The current study introduces an integrated model that combines neighborhood, genetic, and epigenetic factors. Hypotheses were tested with a sample of 99 African American women from the Family and Community Health Study (FACHS). Allele variants of the serotonin transporter gene (5-HTT) interact with neighborhood crime to predict depressive symptoms in a manner consonant with the differential susceptibility perspective. Furthermore, this association is mediated by DNA methylation of the promoter region of the serotonin transporter gene. The findings provide support for an integrated model in which changes in DNA methylation, resulting from neighborhood crime, can result in an increase or decrease in gene activity which, in turn, influences depressive symptoms. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Comprehensive analyses of imprinted differentially methylated regions reveal epigenetic and genetic characteristics in hepatoblastoma

    International Nuclear Information System (INIS)

    Rumbajan, Janette Mareska; Aoki, Shigehisa; Kohashi, Kenichi; Oda, Yoshinao; Hata, Kenichiro; Saji, Tsutomu; Taguchi, Tomoaki; Tajiri, Tatsuro; Soejima, Hidenobu; Joh, Keiichiro; Maeda, Toshiyuki; Souzaki, Ryota; Mitsui, Kazumasa; Higashimoto, Ken; Nakabayashi, Kazuhiko; Yatsuki, Hitomi; Nishioka, Kenichi; Harada, Ryoko

    2013-01-01

    Aberrant methylation at imprinted differentially methylated regions (DMRs) in human 11p15.5 has been reported in many tumors including hepatoblastoma. However, the methylation status of imprinted DMRs in imprinted loci scattered through the human genome has not been analyzed yet in any tumors. The methylation statuses of 33 imprinted DMRs were analyzed in 12 hepatoblastomas and adjacent normal liver tissue by MALDI-TOF MS and pyrosequencing. Uniparental disomy (UPD) and copy number abnormalities were investigated with DNA polymorphisms. Among 33 DMRs analyzed, 18 showed aberrant methylation in at least 1 tumor. There was large deviation in the incidence of aberrant methylation among the DMRs. KvDMR1 and IGF2-DMR0 were the most frequently hypomethylated DMRs. INPP5Fv2-DMR and RB1-DMR were hypermethylated with high frequencies. Hypomethylation was observed at certain DMRs not only in tumors but also in a small number of adjacent histologically normal liver tissue, whereas hypermethylation was observed only in tumor samples. The methylation levels of long interspersed nuclear element-1 (LINE-1) did not show large differences between tumor tissue and normal liver controls. Chromosomal abnormalities were also found in some tumors. 11p15.5 and 20q13.3 loci showed the frequent occurrence of both genetic and epigenetic alterations. Our analyses revealed tumor-specific aberrant hypermethylation at some imprinted DMRs in 12 hepatoblastomas with additional suggestion for the possibility of hypomethylation prior to tumor development. Some loci showed both genetic and epigenetic alterations with high frequencies. These findings will aid in understanding the development of hepatoblastoma

  16. Genetic and epigenetic variation in 5S ribosomal RNA genes reveals genome dynamics in Arabidopsis thaliana.

    Science.gov (United States)

    Simon, Lauriane; Rabanal, Fernando A; Dubos, Tristan; Oliver, Cecilia; Lauber, Damien; Poulet, Axel; Vogt, Alexander; Mandlbauer, Ariane; Le Goff, Samuel; Sommer, Andreas; Duborjal, Hervé; Tatout, Christophe; Probst, Aline V

    2018-04-06

    Organized in tandem repeat arrays in most eukaryotes and transcribed by RNA polymerase III, expression of 5S rRNA genes is under epigenetic control. To unveil mechanisms of transcriptional regulation, we obtained here in depth sequence information on 5S rRNA genes from the Arabidopsis thaliana genome and identified differential enrichment in epigenetic marks between the three 5S rDNA loci situated on chromosomes 3, 4 and 5. We reveal the chromosome 5 locus as the major source of an atypical, long 5S rRNA transcript characteristic of an open chromatin structure. 5S rRNA genes from this locus translocated in the Landsberg erecta ecotype as shown by linkage mapping and chromosome-specific FISH analysis. These variations in 5S rDNA locus organization cause changes in the spatial arrangement of chromosomes in the nucleus. Furthermore, 5S rRNA gene arrangements are highly dynamic with alterations in chromosomal positions through translocations in certain mutants of the RNA-directed DNA methylation pathway and important copy number variations among ecotypes. Finally, variations in 5S rRNA gene sequence, chromatin organization and transcripts indicate differential usage of 5S rDNA loci in distinct ecotypes. We suggest that both the usage of existing and new 5S rDNA loci resulting from translocations may impact neighboring chromatin organization.

  17. Implications of Genetic and Epigenetic Alterations of CDKN2A (p16INK4a in Cancer

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    Ran Zhao

    2016-06-01

    Full Text Available Aberrant gene silencing is highly associated with altered cell cycle regulation during carcinogenesis. In particular, silencing of the CDKN2A tumor suppressor gene, which encodes the p16INK4a protein, has a causal link with several different types of cancers. The p16INK4a protein plays an executional role in cell cycle and senescence through the regulation of the cyclin-dependent kinase (CDK 4/6 and cyclin D complexes. Several genetic and epigenetic aberrations of CDKN2A lead to enhanced tumorigenesis and metastasis with recurrence of cancer and poor prognosis. In these cases, the restoration of genetic and epigenetic reactivation of CDKN2A is a practical approach for the prevention and therapy of cancer. This review highlights the genetic status of CDKN2A as a prognostic and predictive biomarker in various cancers.

  18. Epigenetic rejuvenation.

    Science.gov (United States)

    Manukyan, Maria; Singh, Prim B

    2012-05-01

    Induced pluripotent stem (iPS) cells have provided a rational means of obtaining histo-compatible tissues for 'patient-specific' regenerative therapies (Hanna et al. 2010; Yamanaka & Blau 2010). Despite the obvious potential of iPS cell-based therapies, there are certain problems that must be overcome before these therapies can become safe and routine (Ohi et al. 2011; Pera 2011). As an alternative, we have recently explored the possibility of using 'epigenetic rejuvenation', where the specialized functions of an old cell are rejuvenated in the absence of any change in its differentiated state (Singh & Zacouto 2010). The mechanism(s) that underpin 'epigenetic rejuvenation' are unknown and here we discuss model systems, using key epigenetic modifiers, which might shed light on the processes involved. Epigenetic rejuvenation has advantages over iPS cell techniques that are currently being pursued. First, the genetic and epigenetic abnormalities that arise through the cycle of dedifferentiation of somatic cells to iPS cells followed by redifferentiation of iPS cells into the desired cell type are avoided (Gore et al. 2011; Hussein et al. 2011; Pera 2011): epigenetic rejuvenation does not require passage through the de-/redifferentiation cycle. Second, because the aim of epigenetic rejuvenation is to ensure that the differentiated cell type retains its specialized function it makes redundant the question of transcriptional memory that is inimical to iPS cell-based therapies (Ohi et al. 2011). Third, to produce unrelated cell types using the iPS technology takes a long time, around three weeks, whereas epigenetic rejuvenation of old cells will take only a matter of days. Epigenetic rejuvenation provides the most safe, rapid and cheap route to successful regenerative medicine. © 2012 The Authors. Journal compilation © 2012 by the Molecular Biology Society of Japan/Blackwell Publishing Ltd.

  19. Genetics and epigenetics of small bowel adenocarcinoma: the interactions of CIN, MSI, and CIMP.

    Science.gov (United States)

    Warth, Arne; Kloor, Matthias; Schirmacher, Peter; Bläker, Hendrik

    2011-04-01

    Characterization of tumor genetics and epigenetics allows to stratify a tumor entity according to molecular pathways and may shed light on the interactions of different types of DNA alterations during tumorigenesis. Small intestinal adenocarcinoma is rare, and to date the interrelation of genomic instability and epigenetics has not been investigated in this tumor type. We therefore analyzed 37 primary small bowel carcinomas with known microsatellite instability and KRAS status for chromosomal instability using comparative genomic hybridization, for the presence of aberrant methylation (CpG island methylation phenotype) by methylation-specific polymerase chain reaction, and for BRAF mutations. Chromosomal instability was detected in 22 of 37 (59%) tumors (3 of 9 microsatellite instable, and 19 of 28 microsatellite stable carcinomas). Nine carcinomas (24%) were microsatellite and chromosomally stable. High-level DNA methylation was found in 16% of chromosomal instable tumors and in 44% of both microsatellite instable and microsatellite and chromosomally stable carcinomas. KRAS was mutated in 55, 0, and 10% of chromosomal instable, microsatellite instable, and microsatellite and chromosomally stable tumors, respectively whereas the frequencies of BRAF mutations were 6% for chromosomal instable and 22% for both microsatellite instable and microsatellite and chromosomally stable carcinomas. In conclusion, in this study we show that chromosomal instable carcinomas of the small intestine are distinguished from microsatellite instable and microsatellite and chromosomally stable tumors by a high frequency of KRAS mutations, low frequencies of CpG island methylation phenotype, and BRAF mutations. In microsatellite instable and microsatellite and chromosomally stable cancers, CpG island methylation phenotype and BRAF/KRAS mutations are similarly distributed, indicating common mechanisms of tumor initiation or progression in their molecular pathogenesis.

  20. The Zebrafish Models to Explore Genetic and Epigenetic Impacts on Evolutionary Developmental Origins of Aging

    Science.gov (United States)

    Kishi, Shuji

    2014-01-01

    Can we reset, reprogram, rejuvenate or reverse the organismal aging process? Certain genetic manipulations could at least reset and reprogram epigenetic dynamics beyond phenotypic plasticity and elasticity in cells, which can be further manipulated into organisms. However, in a whole complex aging organism, how can we rejuvenate intrinsic resources and infrastructures in an intact/noninvasive manner? The incidence of diseases increases exponentially with age, accompanied by progressive deteriorations of physiological functions in organisms. Aging-associated diseases are sporadic but essentially inevitable complications arising from senescence. Senescence is often considered the antithesis of early development, but yet there may be factors and mechanisms in common between these two phenomena to rejuvenate over the dynamic process of aging. The association between early development and late-onset disease with advancing age is thought to come from a consequence of developmental plasticity, the phenomenon by which one genotype can give rise to a range of physiologically and/or morphologically adaptive states based on diverse epigenotypes, in response to intrinsic or extrinsic environmental cues and genetic perturbations. We hypothesized that the future aging process can be predictive based on adaptivity during the early developmental period. Modulating the thresholds and windows of plasticity and its robustness by molecular genetic and chemical epigenetic approaches, we have successfully conducted experiments to isolate zebrafish mutants expressing apparently altered senescence phenotypes during their embryonic and/or larval stages (“embryonic/larval senescence”). Subsequently, at least some of these mutant animals were found to show shortened lifespan, while some others would be expected to live longer in adulthoods. We anticipate that previously uncharacterized developmental genes may mediate the aging process and play a pivotal role in senescence. On the other

  1. Cross-tissue integration of genetic and epigenetic data offers insight into autism spectrum disorder.

    Science.gov (United States)

    Andrews, Shan V; Ellis, Shannon E; Bakulski, Kelly M; Sheppard, Brooke; Croen, Lisa A; Hertz-Picciotto, Irva; Newschaffer, Craig J; Feinberg, Andrew P; Arking, Dan E; Ladd-Acosta, Christine; Fallin, M Daniele

    2017-10-24

    Integration of emerging epigenetic information with autism spectrum disorder (ASD) genetic results may elucidate functional insights not possible via either type of information in isolation. Here we use the genotype and DNA methylation (DNAm) data from cord blood and peripheral blood to identify SNPs associated with DNA methylation (meQTL lists). Additionally, we use publicly available fetal brain and lung meQTL lists to assess enrichment of ASD GWAS results for tissue-specific meQTLs. ASD-associated SNPs are enriched for fetal brain (OR = 3.55; P < 0.001) and peripheral blood meQTLs (OR = 1.58; P < 0.001). The CpG targets of ASD meQTLs across cord, blood, and brain tissues are enriched for immune-related pathways, consistent with other expression and DNAm results in ASD, and reveal pathways not implicated by genetic findings. This joint analysis of genotype and DNAm demonstrates the potential of both brain and blood-based DNAm for insights into ASD and psychiatric phenotypes more broadly.

  2. Epigenome-wide association study of DNA methylation in narcolepsy: an integrated genetic and epigenetic approach.

    Science.gov (United States)

    Shimada, Mihoko; Miyagawa, Taku; Toyoda, Hiromi; Tokunaga, Katsushi; Honda, Makoto

    2018-04-01

    Narcolepsy with cataplexy, which is a hypersomnia characterized by excessive daytime sleepiness and cataplexy, is a multifactorial disease caused by both genetic and environmental factors. Several genetic factors including HLA-DQB1*06:02 have been identified; however, the disease etiology is still unclear. Epigenetic modifications, such as DNA methylation, have been suggested to play an important role in the pathogenesis of complex diseases. Here, we examined DNA methylation profiles of blood samples from narcolepsy and healthy control individuals and performed an epigenome-wide association study (EWAS) to investigate methylation loci associated with narcolepsy. Moreover, data from the EWAS and a previously performed narcolepsy genome-wide association study were integrated to search for methylation loci with causal links to the disease. We found that (1) genes annotated to the top-ranked differentially methylated positions (DMPs) in narcolepsy were associated with pathways of hormone secretion and monocarboxylic acid metabolism. (2) Top-ranked narcolepsy-associated DMPs were significantly more abundant in non-CpG island regions and more than 95 per cent of such sites were hypomethylated in narcolepsy patients. (3) The integrative analysis identified the CCR3 region where both a single methylation site and multiple single-nucleotide polymorphisms were found to be associated with the disease as a candidate region responsible for narcolepsy. The findings of this study suggest the importance of future replication studies, using methylation technologies with wider genome coverage and/or larger number of samples, to confirm and expand on these results.

  3. Detection vs. selection: integration of genetic, epigenetic and environmental cues in fluctuating environments.

    Science.gov (United States)

    McNamara, John M; Dall, Sasha R X; Hammerstein, Peter; Leimar, Olof

    2016-10-01

    There are many inputs during development that influence an organism's fit to current or upcoming environments. These include genetic effects, transgenerational epigenetic influences, environmental cues and developmental noise, which are rarely investigated in the same formal framework. We study an analytically tractable evolutionary model, in which cues are integrated to determine mature phenotypes in fluctuating environments. Environmental cues received during development and by the mother as an adult act as detection-based (individually observed) cues. The mother's phenotype and a quantitative genetic effect act as selection-based cues (they correlate with environmental states after selection). We specify when such cues are complementary and tend to be used together, and when using the most informative cue will predominate. Thus, we extend recent analyses of the evolutionary implications of subsets of these effects by providing a general diagnosis of the conditions under which detection and selection-based influences on development are likely to evolve and coexist. © 2016 John Wiley & Sons Ltd/CNRS.

  4. Genetic, environmental, and epigenetic factors in the development of personality disturbance.

    Science.gov (United States)

    Depue, Richard A

    2009-01-01

    A dimensional model of personality disturbance is presented that is defined by extreme values on interacting subsets of seven major personality traits. Being at the extreme has marked effects on the threshold for eliciting those traits under stimulus conditions: that is, the extent to which the environment affects the neurobiological functioning underlying the traits. To explore the nature of development of extreme values on these traits, each trait is discussed in terms of three major issues: (a) the neurobiological variables associated with the trait, (b) individual variation in this neurobiology as a function of genetic polymorphisms, and (c) the effects of environmental adversity on these neurobiological variables through the action of epigenetic processes. It is noted that gene-environment interaction appears to be dependent on two main factors: (a) both genetic and environmental variables appear to have the most profound and enduring effects when they exert their effects during early postnatal periods, times when the forebrain is undergoing exuberant experience-expectant dendritic and axonal growth; and (b) environmental effects on neurobiology are strongly modified by individual differences in "traitlike" functioning of neurobiological variables. A model of the nature of the interaction between environmental and neurobiological variables in the development of personality disturbance is presented.

  5. Genetic and epigenetic features in radiation sensitivity. Part II: implications for clinical practice and radiation protection

    International Nuclear Information System (INIS)

    Bourguignon, Michel H.; Gisone, Pablo A.; Perez, Maria R.; Michelin, Severino; Dubner, Diana; Giorgio, Marina di; Carosella, Edgardo D.

    2005-01-01

    Recent progress especially in the field of gene identification and expression has attracted greater attention to the genetic and epigenetic susceptibility to cancer, possibly enhanced by ionising radiation. This issue is especially important for radiation therapists since hypersensitive patients may suffer from adverse effects in normal tissues following standard radiation therapy, while normally sensitive patients could receive higher doses of radiation, offering a better likelihood of cure for malignant tumours. Although only a small percentage of individuals are ''hypersensitive'' to radiation effects, all medical specialists using ionising radiation should be aware of the aforementioned progress in medical knowledge. The present paper, the second of two parts, reviews human disorders known or strongly suspected to be associated with hypersensitivity to ionising radiation. The main tests capable of detecting such pathologies in advance are analysed, and ethical issues regarding genetic testing are considered. The implications for radiation protection of possible hypersensitivity to radiation in a part of the population are discussed, and some guidelines for nuclear medicine professionals are proposed. (orig.)

  6. Individual Differences in Social Behavior and Cortical Vasopressin Receptor: Genetics, Epigenetics, and Evolution

    Directory of Open Access Journals (Sweden)

    Steven M. Phelps

    2017-10-01

    Full Text Available Social behavior is among the most complex and variable of traits. Despite its diversity, we know little about how genetic and developmental factors interact to shape natural variation in social behavior. This review surveys recent work on individual differences in the expression of the vasopressin 1a receptor (V1aR, a major regulator of social behavior, in the neocortex of the socially monogamous prairie vole. V1aR exhibits profound variation in the retrosplenial cortex (RSC, a region critical to spatial and contextual memory. RSC-V1aR abundance is associated with patterns of male space-use and sexual fidelity in the field: males with high RSC-V1aR show high spatial and sexual fidelity to partners, while low RSC-V1aR males are significantly more likely to mate outside the pair-bond. Individual differences in RSC-V1aR are predicted by a set of linked single nucleotide polymorphisms within the avpr1a locus. These alternative alleles have been actively maintained by selection, suggesting that the brain differences represent a balanced polymorphism. Lastly, the alleles occur within regulatory sequences, and result in differential sensitivity to environmental perturbation. Together the data provide insight into how genetic, epigenetic and evolutionary forces interact to shape the social brain.

  7. What Is Direct-to-Consumer Genetic Testing?

    Science.gov (United States)

    ... consumer genetic testing? What kinds of direct-to-consumer genetic tests are available? What is genetic ancestry testing? What are the benefits and risks of direct-to-consumer genetic testing? ...

  8. Genetic control of an epigenetic cell degeneration syndrome in Podospora anserina.

    Science.gov (United States)

    Haedens, Vicki; Malagnac, Fabienne; Silar, Philippe

    2005-06-01

    Filamentous fungi frequently present degenerative processes, whose molecular basis is very often unknown. Here, we present three mutant screens that result in the identification of 29 genes that directly or indirectly control Crippled Growth (CG), an epigenetic cell degeneration of the filamentous ascomycete Podospora anserina. Two of these genes were previously shown to encode a MAP kinase kinase kinase and an NADPH oxidase involved in a signal transduction cascade that participates in stationary phase differentiations, fruiting body development and defence against fungal competitors. The numerous genes identified can be incorporated in a model in which CG results from the sustained activation of the MAP kinase cascade. Our data also emphasize the complex regulatory network underlying three interconnected processes in P. anserina: sexual reproduction, defence against competitors, and cell degeneration.

  9. Genetic and epigenetic inactivation of SESTRIN1 controls mTORC1 and response to EZH2 inhibition in follicular lymphoma.

    Science.gov (United States)

    Oricchio, Elisa; Katanayeva, Natalya; Donaldson, Maria Christine; Sungalee, Stephanie; Pasion, Joyce P; Béguelin, Wendy; Battistello, Elena; Sanghvi, Viraj R; Jiang, Man; Jiang, Yanwen; Teater, Matt; Parmigiani, Anita; Budanov, Andrei V; Chan, Fong Chun; Shah, Sohrab P; Kridel, Robert; Melnick, Ari M; Ciriello, Giovanni; Wendel, Hans-Guido

    2017-06-28

    Follicular lymphoma (FL) is an incurable form of B cell lymphoma. Genomic studies have cataloged common genetic lesions in FL such as translocation t(14;18), frequent losses of chromosome 6q, and mutations in epigenetic regulators such as EZH2 Using a focused genetic screen, we identified SESTRIN1 as a relevant target of the 6q deletion and demonstrate tumor suppression by SESTRIN1 in vivo. Moreover, SESTRIN1 is a direct target of the lymphoma-specific EZH2 gain-of-function mutation ( EZH2 Y641X ). SESTRIN1 inactivation disrupts p53-mediated control of mammalian target of rapamycin complex 1 (mTORC1) and enables mRNA translation under genotoxic stress. SESTRIN1 loss represents an alternative to RRAGC mutations that maintain mTORC1 activity under nutrient starvation. The antitumor efficacy of pharmacological EZH2 inhibition depends on SESTRIN1, indicating that mTORC1 control is a critical function of EZH2 in lymphoma. Conversely, EZH2 Y641X mutant lymphomas show increased sensitivity to RapaLink-1, a bifunctional mTOR inhibitor. Hence, SESTRIN1 contributes to the genetic and epigenetic control of mTORC1 in lymphoma and influences responses to targeted therapies. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  10. Integrative analysis reveals relationships of genetic and epigenetic alterations in osteosarcoma.

    Directory of Open Access Journals (Sweden)

    Stine H Kresse

    Full Text Available BACKGROUND: Osteosarcomas are the most common non-haematological primary malignant tumours of bone, and all conventional osteosarcomas are high-grade tumours showing complex genomic aberrations. We have integrated genome-wide genetic and epigenetic profiles from the EuroBoNeT panel of 19 human osteosarcoma cell lines based on microarray technologies. PRINCIPAL FINDINGS: The cell lines showed complex patterns of DNA copy number changes, where genomic copy number gains were significantly associated with gene-rich regions and losses with gene-poor regions. By integrating the datasets, 350 genes were identified as having two types of aberrations (gain/over-expression, hypo-methylation/over-expression, loss/under-expression or hyper-methylation/under-expression using a recurrence threshold of 6/19 (>30% cell lines. The genes showed in general alterations in either DNA copy number or DNA methylation, both within individual samples and across the sample panel. These 350 genes are involved in embryonic skeletal system development and morphogenesis, as well as remodelling of extracellular matrix. The aberrations of three selected genes, CXCL5, DLX5 and RUNX2, were validated in five cell lines and five tumour samples using PCR techniques. Several genes were hyper-methylated and under-expressed compared to normal osteoblasts, and expression could be reactivated by demethylation using 5-Aza-2'-deoxycytidine treatment for four genes tested; AKAP12, CXCL5, EFEMP1 and IL11RA. Globally, there was as expected a significant positive association between gain and over-expression, loss and under-expression as well as hyper-methylation and under-expression, but gain was also associated with hyper-methylation and under-expression, suggesting that hyper-methylation may oppose the effects of increased copy number for detrimental genes. CONCLUSIONS: Integrative analysis of genome-wide genetic and epigenetic alterations identified dependencies and relationships between

  11. Genetic and epigenetic regulatory mechanisms of the oxytocin receptor gene (OXTR) and the (clinical) implications for social behavior.

    Science.gov (United States)

    Tops, Sanne; Habel, Ute; Radke, Sina

    2018-03-12

    Oxytocin and the oxytocin receptor (OXTR) play an important role in a large variety of social behaviors. The oxytocinergic system interacts with environmental cues and is highly dependent on interindividual factors. Deficits in this system have been linked to mental disorders associated with social impairments, such as autism spectrum disorder (ASD). This review focuses on the modulation of social behavior by alterations in two domains of the oxytocinergic system. We discuss genetic and epigenetic regulatory mechanisms and alterations in these mechanisms that were found to have clinical implications for ASD. We propose possible explanations how these alterations affect the biological pathways underlying the aberrant social behavior and point out avenues for future research. We advocate the need for integration studies that combine multiple measures covering a broad range of social behaviors and link these to genetic and epigenetic profiles. Copyright © 2018. Published by Elsevier Inc.

  12. Genetic and epigenetic alterations of the reduced folate carrier in untreated diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Kastrup, I.B.; Worm, J.; Ralfkiaer, E.

    2008-01-01

    The reduced folate carrier (RFC) is a transmembrane protein that mediates cellular uptake of reduced folates and antifolate drugs, including methotrexate (MTX). Acquired alterations of the RFC gene have been associated with resistance to MTX in cancer cell lines and primary osteosarcomas. Here, w...... with adverse outcome. In DLBCL, genetic and epigenetic alterations of RFC were detected at diagnosis in the absence of a selective MTX pressure, suggesting that these alterations may possibly contribute to the development of lymphoma Udgivelsesdato: 2008/1...

  13. Epigenetic variation contributes to environmental adaptation of Arabidopsis thaliana

    NARCIS (Netherlands)

    Kooke, R.; Keurentjes, J.J.B.

    2015-01-01

    Epigenetic variation is frequently observed in plants and direct relationships between differences in DNA methylation and phenotypic responses to changing environments have often been described. The identification of contributing genetic loci, however, was until recently hampered by the lack of

  14. Genetic and epigenetic alteration among three homoeologous genes of a class E MADS box gene in hexaploid wheat.

    Science.gov (United States)

    Shitsukawa, Naoki; Tahira, Chikako; Kassai, Ken-Ichiro; Hirabayashi, Chizuru; Shimizu, Tomoaki; Takumi, Shigeo; Mochida, Keiichi; Kawaura, Kanako; Ogihara, Yasunari; Murai, Koji

    2007-06-01

    Bread wheat (Triticum aestivum) is a hexaploid species with A, B, and D ancestral genomes. Most bread wheat genes are present in the genome as triplicated homoeologous genes (homoeologs) derived from the ancestral species. Here, we report that both genetic and epigenetic alterations have occurred in the homoeologs of a wheat class E MADS box gene. Two class E genes are identified in wheat, wheat SEPALLATA (WSEP) and wheat LEAFY HULL STERILE1 (WLHS1), which are homologs of Os MADS45 and Os MADS1 in rice (Oryza sativa), respectively. The three wheat homoeologs of WSEP showed similar genomic structures and expression profiles. By contrast, the three homoeologs of WLHS1 showed genetic and epigenetic alterations. The A genome WLHS1 homoeolog (WLHS1-A) had a structural alteration that contained a large novel sequence in place of the K domain sequence. A yeast two-hybrid analysis and a transgenic experiment indicated that the WLHS1-A protein had no apparent function. The B and D genome homoeologs, WLHS1-B and WLHS1-D, respectively, had an intact MADS box gene structure, but WLHS1-B was predominantly silenced by cytosine methylation. Consequently, of the three WLHS1 homoeologs, only WLHS1-D functions in hexaploid wheat. This is a situation where three homoeologs are differentially regulated by genetic and epigenetic mechanisms.

  15. Is Neurofibromatosis Type 1-Noonan Syndrome a Phenotypic Result of Combined Genetic and Epigenetic Factors?

    Science.gov (United States)

    Yapijakis, Christos; Pachis, Nikos; Natsis, Stavros; Voumvourakis, Costas

    2016-01-01

    Neurofibromatosis 1-Noonan syndrome (NFNS) presents combined characteristics of both autosomal dominant disorders: NF1 and Noonan syndrome (NS). The genes causing NF1 and NS are located on different chromosomes, making it uncertain whether NFNS is a separate entity as previously suggested, or rather a clinical variation. We present a four-membered Greek family. The father was diagnosed with familial NF1 and the mother with generalized epilepsy, being under hydantoin treatment since the age of 18 years. Their two male children exhibited NFNS characteristics. The father and his sons shared R1947X mutation in the NF1 gene. The two children with NFNS phenotype presented with NF1 signs inherited from their father and fetal hydantoin syndrome-like phenotype due to exposure to that anticonvulsant during fetal development. The NFNS phenotype may be the result of both a genetic factor (mutation in the NF1 gene) and an epigenetic/environmental factor (e.g. hydantoin). Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  16. Genetic and Epigenetic Inactivation of Kruppel-like Factor 4 in Medulloblastoma

    Directory of Open Access Journals (Sweden)

    Yukiko Nakahara

    2010-01-01

    Full Text Available Although medulloblastoma is the most common pediatric malignant brain tumor, its molecular underpinnings are largely unknown. We have identified rare, recurrent homozygous deletions of Kruppel-like Factor 4 (KLF4 in medulloblastoma using high-resolution single nucleotide polymorphism arrays, digital karyotyping, and genomic real-time polymerase chain reaction (PCR. Furthermore, we show that there is loss of physiological KLF4 expression in more than 40% of primary medulloblastomas both at the RNA and protein levels. Medulloblastoma cell lines drastically increase the expression of KLF4 in response to the demethylating agent 5-azacytidine and demonstrate dense methylation of the promoter CpG island by bisulfite sequencing. Methylation-specific PCR targeting the KLF4 promoter demonstrates CpG methylation in approximately 16% of primary medulloblastomas. Reexpression of KLF4 in the D283 medulloblastoma cell line results in significant growth suppression both in vitro and in vivo. We conclude that KLF4 is inactivated by either genetic or epigenetic mechanisms in a large subset of medulloblastomas and that it likely functions as a tumor suppressor gene in the pathogenesis of medulloblastoma.

  17. Epigenetics in adaptive evolution and development: the interplay between evolving species and epigenetic mechanisms: extract from Trygve Tollefsbol (ed.) (2011) Handbook of epigenetics--the new molecular and medical genetics. Chapter 26. Amsterdam, USA: Elsevier, pp. 423-446.

    Science.gov (United States)

    House, Simon H

    2013-04-01

    By comparing epigenetics of current species with fossil records across evolutionary transitions, we can gauge the moment of emergence of some novel mechanisms in evolution, and recognize that epigenetic mechanisms have a bearing on mutation. Understanding the complexity and changeability of these mechanisms, as well as the changes they can effect, is both fascinating and of vital practical benefit. Our most serious pandemics of so-called 'non-communicable' diseases - mental and cardiovascular disorders, obesity and diabetes, rooted in the 'metabolic syndrome' - are evidently related to effects on our evolutionary mechanisms of agricultural and food industrialization, modern lifestyle and diet. Pollution affects us directly as well as indirectly by its destruction of ecologically essential biosystems. Evidently such powerful conditions of existence have epigenetic effects on both our health and our continuing evolution. Such effects are most profound during reproductive and developmental processes, when levels of hormones, as affected by stress particularly, may be due to modern cultures in childbearing such as excessive intervention, separation, maternal distress and disruption of bonding. Mechanisms of genomic imprinting seem likely to throw light on problems in assisted reproductive technology, among other transgenerational effects. © The Author(s) 2014.

  18. Epigenetics: beyond genes

    CSIR Research Space (South Africa)

    Fossey, A

    2009-06-01

    Full Text Available in forestry breeding. Keywords Gene regulation; chromatin; histone code hyporthesis; RNA silencing; post transcriptional gene silencing; forestry. Introduction to epigenetic phenomena Most living organisms share a vast amount of genetic information... (Rapp and Wendel, 2005). Epigenetic phenomena pervade all aspects of cell proliferation and plant development and are often in conflict with Mendelian models of genetics (Grant-Downton and Dickinson, 2005). A key element in many epigenetic effects...

  19. Epigenetics and Colorectal Cancer

    Science.gov (United States)

    Lao, Victoria Valinluck; Grady, William M.

    2012-01-01

    Colorectal cancer is a leading cause of cancer deaths in the world. It results from an accumulation of genetic and epigenetic changes in colon epithelial cells that transforms them into adenocarcinomas. There have been major advances in our understanding of cancer epigenetics over the last decade, particularly regarding aberrant DNA methylation. Assessment of the colon cancer epigenome has revealed that virtually all colorectal cancers have aberrantly methylated genes and the average colorectal cancer methylome has hundreds to thousands of abnormally methylated genes. As with gene mutations in the cancer genome, a subset of these methylated genes, called driver genes, is presumed to play a functional role in colorectal cancer. The assessment of methylated genes in colorectal cancers has also revealed a unique molecular subgroup of colorectal cancers called CpG Island Methylator Phenotype (CIMP) cancers; these tumors have a particularly high frequency of methylated genes. The advances in our understanding of aberrant methylation in colorectal cancer has led to epigenetic alterations being developed as clinical biomarkers for diagnostic, prognostic, and therapeutic applications. Progress in the assessment of epigenetic alterations in colorectal cancer and their clinical applications has shown that these alterations will be commonly used in the near future as molecular markers to direct the prevention and treatment of colorectal cancer. PMID:22009203

  20. Epigenetic and epistatic interactions between serotonin transporter and brain-derived neurotrophic factor genetic polymorphism: insights in depression.

    Science.gov (United States)

    Ignácio, Z M; Réus, G Z; Abelaira, H M; Quevedo, J

    2014-09-05

    Epidemiological studies have shown significant results in the interaction between the functions of brain-derived neurotrophic factor (BDNF) and 5-HT in mood disorders, such as major depressive disorder (MDD). The latest research has provided convincing evidence that gene transcription of these molecules is a target for epigenetic changes, triggered by stressful stimuli that starts in early childhood and continues throughout life, which are subsequently translated into structural and functional phenotypes culminating in depressive disorders. The short variants of 5-HTTLPR and BDNF-Met are seen as forms which are predisposed to epigenetic aberrations, which leads individuals to a susceptibility to environmental adversities, especially when subjected to stress in early life. Moreover, the polymorphic variants also feature epistatic interactions in directing the functional mechanisms elicited by stress and underlying the onset of depressive disorders. Also emphasized are works which show some mediators between stress and epigenetic changes of the 5-HTT and BDNF genes, such as the hypothalamic-pituitary-adrenal (HPA) axis and the cAMP response element-binding protein (CREB), which is a cellular transcription factor. Both the HPA axis and CREB are also involved in epistatic interactions between polymorphic variants of 5-HTTLPR and Val66Met. This review highlights some research studying changes in the epigenetic patterns intrinsic to genes of 5-HTT and BDNF, which are related to lifelong environmental adversities, which in turn increases the risks of developing MDD. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  1. Landscaping plant epigenetics.

    Science.gov (United States)

    McKeown, Peter C; Spillane, Charles

    2014-01-01

    The understanding of epigenetic mechanisms is necessary for assessing the potential impacts of epigenetics on plant growth, development and reproduction, and ultimately for the response of these factors to evolutionary pressures and crop breeding programs. This volume highlights the latest in laboratory and bioinformatic techniques used for the investigation of epigenetic phenomena in plants. Such techniques now allow genome-wide analyses of epigenetic regulation and help to advance our understanding of how epigenetic regulatory mechanisms affect cellular and genome function. To set the scene, we begin with a short background of how the field of epigenetics has evolved, with a particular focus on plant epigenetics. We consider what has historically been understood by the term "epigenetics" before turning to the advances in biochemistry, molecular biology, and genetics which have led to current-day definitions of the term. Following this, we pay attention to key discoveries in the field of epigenetics that have emerged from the study of unusual and enigmatic phenomena in plants. Many of these phenomena have involved cases of non-Mendelian inheritance and have often been dismissed as mere curiosities prior to the elucidation of their molecular mechanisms. In the penultimate section, consideration is given to how advances in molecular techniques are opening the doors to a more comprehensive understanding of epigenetic phenomena in plants. We conclude by assessing some opportunities, challenges, and techniques for epigenetic research in both model and non-model plants, in particular for advancing understanding of the regulation of genome function by epigenetic mechanisms.

  2. New insights in oncology: Epi-genetics and cancer stem cells; Nouvelles perspectives en oncologie: epigenetique et cellules souches cancereuses

    Energy Technology Data Exchange (ETDEWEB)

    Krutovskikh, V.; Partensky, C. [Centre international de recherche sur le cancer, 150, cours Albert-Thomas, 69372 Lyon cedex 08 (France)

    2011-12-15

    Cancer is a multi-etiologic, multistage disease with a prevalent genetic component, which happens when a large number of genes, critical for cell growth, death, differentiation, migration, and metabolic plasticity are altered irreversibly, so as to either 'gain' (oncogenes) or 'lose' (tumour suppressors) their function. Recent discoveries have revealed the previously underestimated etiologic importance of multiple epigenetic, that is to say, reversible factors (histone modifications, DNA methylation, non-coding RNA) involved in the transcriptional and post-transcriptional regulation of proteins, indispensable for the control of cancerous phenotype. Stable alterations of epigenetic machinery ('epi-mutations') turn out to play a critical role at different steps of carcinogenesis. In addition, due to substantial recent progress in stem cell biology, the new concept of cancer stem cells has emerged. This, along with newly discovered epigenetic cancer mechanisms, gives rise to a hope to overcome radio- and chemo-resistance and to eradicate otherwise incurable neoplasms. (authors)

  3. Altered expression of MGMT in high-grade gliomas results from the combined effect of epigenetic and genetic aberrations.

    Directory of Open Access Journals (Sweden)

    João Ramalho-Carvalho

    Full Text Available MGMT downregulation in high-grade gliomas (HGG has been mostly attributed to aberrant promoter methylation and is associated with increased sensitivity to alkylating agent-based chemotherapy. However, HGG harboring 10q deletions also benefit from treatment with alkylating agents. Because the MGMT gene is mapped at 10q26, we hypothesized that both epigenetic and genetic alterations might affect its expression and predict response to chemotherapy. To test this hypothesis, promoter methylation and mRNA levels of MGMT were determined by quantitative methylation-specific PCR (qMSP or methylation-specific multiplex ligation dependent probe amplification (MS-MLPA and quantitative RT-PCR, respectively, in a retrospective series of 61 HGG. MGMT/chromosome 10 copy number variations were determined by FISH or MS-MLPA analysis. Molecular findings were correlated with clinical parameters to assess their predictive value. Overall, MGMT methylation ratios assessed by qMSP and MS-MLPA were inversely correlated with mRNA expression levels (best coefficient value obtained with MS-MLPA. By FISH analysis in 68.3% of the cases there was loss of 10q26.1 and in 15% of the cases polysomy was demonstrated; the latter displayed the highest levels of transcript. When genetic and epigenetic data were combined, cases with MGMT promoter methylation and MGMT loss depicted the lowest transcript levels, although an impact in response to alkylating agent chemotherapy was not apparent. Cooperation between epigenetic (promoter methylation and genetic (monosomy, locus deletion changes affecting MGMT in HGG is required for effective MGMT silencing. Hence, evaluation of copy number alterations might add relevant prognostic and predictive information concerning response to alkylating agent-based chemotherapy.

  4. Abnormal genetic and epigenetic changes in signal transducer and activator of transcription 4 in the pathogenesis of inflammatory bowel diseases.

    Science.gov (United States)

    Kim, Seung Won; Kim, Eun Soo; Moon, Chang Mo; Kim, Tae Il; Kim, Won Ho; Cheon, Jae Hee

    2012-10-01

    Changes in the expression of signal transducer and activator of transcription 4 (STAT4) contribute to the development of a variety of autoimmune diseases including inflammatory bowel diseases (IBDs). Moreover, epigenetic modifications, including DNA methylation, are considered a basis for differentiation of T helper cells and regulation of cytokines. In this study, we investigated the methylation status of STAT4 gene in IBD patients and the associations between its genetic and epigenetic alterations in IBD patients. Blood and colonic mucosa samples were obtained from Korean patients with IBD and healthy controls. Peripheral blood mononuclear cells (PBMCs) were isolated, and total RNA and genomic DNA were isolated from the PBMCs and colon mucosa tissues. The mRNA level and DNA methylation status of the promoter were determined by real-time RT-PCR and pyrosequencing, respectively. The chosen SNPs (rs11889341, rs7574865, rs8179673, rs6752770, rs925847, rs10168266, rs10181656, and rs11685878) were genotyped using the TaqMan nuclease assay. Elevated expression of STAT4 was observed in the colonic mucosa and PBMCs of IBD patients. IBD patients showed a lower degree of methylation of the STAT4 promoter than did the healthy controls. Moreover, a significant correlation between risk alleles and methylation status at -172 of the STAT4 promoter was observed, and mRNA levels of STAT4 in IBD patients were correlated inversely with the T-risk allele (rs7574865). Our data demonstrated that the DNA methylation status of STAT4 is associated with genetic polymorphisms, providing insights into the interactions between genetic and epigenetic aberrances in STAT4 that contribute to the development of IBD.

  5. Epigenetic Variance, Performing Cooperative Structure with Genetics, Is Associated with Leaf Shape Traits in Widely Distributed Populations of Ornamental Tree Prunus mume

    Directory of Open Access Journals (Sweden)

    Kaifeng Ma

    2018-01-01

    Full Text Available Increasing evidence shows that epigenetics plays an important role in phenotypic variance. However, little is known about epigenetic variation in the important ornamental tree Prunus mume. We used amplified fragment length polymorphism (AFLP and methylation-sensitive amplified polymorphism (MSAP techniques, and association analysis and sequencing to investigate epigenetic variation and its relationships with genetic variance, environment factors, and traits. By performing leaf sampling, the relative total methylation level (29.80% was detected in 96 accessions of P. mume. And the relative hemi-methylation level (15.77% was higher than the relative full methylation level (14.03%. The epigenetic diversity (I∗ = 0.575, h∗ = 0.393 was higher than the genetic diversity (I = 0.484, h = 0.319. The cultivated population displayed greater epigenetic diversity than the wild populations in both southwest and southeast China. We found that epigenetic variance and genetic variance, and environmental factors performed cooperative structures, respectively. In particular, leaf length, width and area were positively correlated with relative full methylation level and total methylation level, indicating that the DNA methylation level played a role in trait variation. In total, 203 AFLP and 423 MSAP associated markers were detected and 68 of them were sequenced. Homologous analysis and functional prediction suggested that the candidate marker-linked genes were essential for leaf morphology development and metabolism, implying that these markers play critical roles in the establishment of leaf length, width, area, and ratio of length to width.

  6. Epigenetic Variance, Performing Cooperative Structure with Genetics, Is Associated with Leaf Shape Traits in Widely Distributed Populations of Ornamental Tree Prunus mume.

    Science.gov (United States)

    Ma, Kaifeng; Sun, Lidan; Cheng, Tangren; Pan, Huitang; Wang, Jia; Zhang, Qixiang

    2018-01-01

    Increasing evidence shows that epigenetics plays an important role in phenotypic variance. However, little is known about epigenetic variation in the important ornamental tree Prunus mume . We used amplified fragment length polymorphism (AFLP) and methylation-sensitive amplified polymorphism (MSAP) techniques, and association analysis and sequencing to investigate epigenetic variation and its relationships with genetic variance, environment factors, and traits. By performing leaf sampling, the relative total methylation level (29.80%) was detected in 96 accessions of P . mume . And the relative hemi-methylation level (15.77%) was higher than the relative full methylation level (14.03%). The epigenetic diversity ( I ∗ = 0.575, h ∗ = 0.393) was higher than the genetic diversity ( I = 0.484, h = 0.319). The cultivated population displayed greater epigenetic diversity than the wild populations in both southwest and southeast China. We found that epigenetic variance and genetic variance, and environmental factors performed cooperative structures, respectively. In particular, leaf length, width and area were positively correlated with relative full methylation level and total methylation level, indicating that the DNA methylation level played a role in trait variation. In total, 203 AFLP and 423 MSAP associated markers were detected and 68 of them were sequenced. Homologous analysis and functional prediction suggested that the candidate marker-linked genes were essential for leaf morphology development and metabolism, implying that these markers play critical roles in the establishment of leaf length, width, area, and ratio of length to width.

  7. Targeting epigenetics for the treatment of prostate cancer: recent progress and future directions.

    Science.gov (United States)

    Lin, Jianqing; Wang, Chenguang; Kelly, Wm Kevin

    2013-06-01

    Epigenetic aberrations contribute to prostate cancer carcinogenesis and disease progression. Efforts have been made to target DNA methyltransferase and histone deacetylases (HDACs) in prostate cancer and other solid tumors but have not had the success that was seen in the hematologic malignancies. Oral, less toxic, and more specific agents are being developed in solid tumors including prostate cancer. Combinations of epigenetic agents alone or with a targeted agent such as androgen receptor signaling inhibitors are promising approaches and will be discussed further. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Behavioral epigenetics.

    Science.gov (United States)

    Moore, David S

    2017-01-01

    Why do we grow up to have the traits we do? Most 20th century scientists answered this question by referring only to our genes and our environments. But recent discoveries in the emerging field of behavioral epigenetics have revealed factors at the interface between genes and environments that also play crucial roles in development. These factors affect how genes work; scientists now know that what matters as much as which genes you have (and what environments you encounter) is how your genes are affected by their contexts. The discovery that what our genes do depends in part on our experiences has shed light on how Nature and Nurture interact at the molecular level inside of our bodies. Data emerging from the world's behavioral epigenetics laboratories support the idea that a person's genes alone cannot determine if, for example, he or she will end up shy, suffering from cardiovascular disease, or extremely smart. Among the environmental factors that can influence genetic activity are parenting styles, diets, and social statuses. In addition to influencing how doctors treat diseases, discoveries about behavioral epigenetics are likely to alter how biologists think about evolution, because some epigenetic effects of experience appear to be transmissible from generation to generation. This domain of research will likely change how we think about the origins of human nature. WIREs Syst Biol Med 2017, 9:e1333. doi: 10.1002/wsbm.1333 For further resources related to this article, please visit the WIREs website. © 2016 Wiley Periodicals, Inc.

  9. Oxytocin Receptor Genetic and Epigenetic Variations: Association with Child Abuse and Adult Psychiatric Symptoms

    Science.gov (United States)

    Smearman, Erica L.; Almli, Lynn M.; Conneely, Karen N.; Brody, Gene H.; Sales, Jessica M.; Bradley, Bekh; Ressler, Kerry J.; Smith, Alicia K.

    2016-01-01

    Childhood abuse can alter biological systems and increase risk for adult psychopathology. Epigenetic mechanisms, alterations in DNA structure that regulate the gene expression, are a potential mechanism underlying this risk. While abuse associates with methylation of certain genes, particularly those in the stress response system, no study to date…

  10. Recent progress in the genetics and epigenetics of paraoxonase: why it is relevant to children’s environmental health

    Science.gov (United States)

    Holland, N; Lizarraga, D; Huen, K

    2015-01-01

    Purpose of review Children are more susceptible to exposures in utero and during early childhood that may result in developmental problems and chronic diseases. Novel discoveries in the field of molecular epidemiology which can help explain susceptibility to exposures and disease will be demonstrated using the multifunctional enzyme paraoxonase (PON1) as an example. Recent findings The broad PON1 variability in humans, partly due to differences in genetics and age, can confer differential susceptibility because this enzyme can detoxify organophosphate pesticides and has antioxidant properties. Epigenetics plays a significant role in the mediation of the effects of environmental exposure on human health and is hypothesized to be a major contributing factor to the early-life origins of adult disease. Studies highlighted in this review demonstrate the relationship of PON1 polymorphisms with microRNA binding in addition to a link between DNA methylation in the transcriptional regulatory region with changes in PON1 enzyme levels. Other important methodologies such as ancestry informative markers and lactonase activity can enhance studies involving PON1. Summary This PON1 model demonstrates that integrating genetic and epigenetic factors as well as other novel methodologies can improve our understanding of important susceptibility factors linked to pediatric disease. PMID:25635583

  11. Epigenetics and cancer

    DEFF Research Database (Denmark)

    Lund, Anders H; van Lohuizen, Maarten

    2004-01-01

    Epigenetic mechanisms act to change the accessibility of chromatin to transcriptional regulation locally and globally via modifications of the DNA and by modification or rearrangement of nucleosomes. Epigenetic gene regulation collaborates with genetic alterations in cancer development. This is e......Epigenetic mechanisms act to change the accessibility of chromatin to transcriptional regulation locally and globally via modifications of the DNA and by modification or rearrangement of nucleosomes. Epigenetic gene regulation collaborates with genetic alterations in cancer development....... This is evident from every aspect of tumor biology including cell growth and differentiation, cell cycle control, DNA repair, angiogenesis, migration, and evasion of host immunosurveillance. In contrast to genetic cancer causes, the possibility of reversing epigenetic codes may provide new targets for therapeutic...

  12. Identification of genes associated with dissociation of cognitive performance and neuropathological burden: Multistep analysis of genetic, epigenetic, and transcriptional data.

    Directory of Open Access Journals (Sweden)

    Charles C White

    2017-04-01

    Full Text Available The molecular underpinnings of the dissociation of cognitive performance and neuropathological burden are poorly understood, and there are currently no known genetic or epigenetic determinants of the dissociation."Residual cognition" was quantified by regressing out the effects of cerebral pathologies and demographic characteristics on global cognitive performance proximate to death. To identify genes influencing residual cognition, we leveraged neuropathological, genetic, epigenetic, and transcriptional data available for deceased participants of the Religious Orders Study (n = 492 and the Rush Memory and Aging Project (n = 487. Given that our sample size was underpowered to detect genome-wide significance, we applied a multistep approach to identify genes influencing residual cognition, based on our prior observation that independent genetic and epigenetic risk factors can converge on the same locus. In the first step (n = 979, we performed a genome-wide association study with a predefined suggestive p < 10-5, and nine independent loci met this threshold in eight distinct chromosomal regions. Three of the six genes within 100 kb of the lead SNP are expressed in the dorsolateral prefrontal cortex (DLPFC: UNC5C, ENC1, and TMEM106B. In the second step, in the subset of participants with DLPFC DNA methylation data (n = 648, we found that residual cognition was related to differential DNA methylation of UNC5C and ENC1 (false discovery rate < 0.05. In the third step, in the subset of participants with DLPFC RNA sequencing data (n = 469, brain transcription levels of UNC5C and ENC1 were evaluated for their association with residual cognition: RNA levels of both UNC5C (estimated effect = -0.40, 95% CI -0.69 to -0.10, p = 0.0089 and ENC1 (estimated effect = 0.0064, 95% CI 0.0033 to 0.0096, p = 5.7 × 10-5 were associated with residual cognition. In secondary analyses, we explored the mechanism of these associations and found that ENC1 may be related to

  13. Genetic and epigenetic diversity and structure of Phragmites australis from local habitats of the Songnen Prairie using amplified fragment length polymorphism markers.

    Science.gov (United States)

    Qiu, T; Jiang, L L; Yang, Y F

    2016-08-19

    The genetic and epigenetic diversity and structure of naturally occurring Phragmites australis populations occupying two different habitats on a small spatial scale in the Songnen Prairie in northeastern China were investigated by assessing amplified fragment length polymorphisms (AFLPs) and methylation-sensitive amplified polymorphisms (MSAPs) through fluorescent capillary detection. The two groups of P. australis were located in a seasonal waterlogged low-lying and alkalized meadow with a pH of 8-8.5 and in an alkaline patch without accumulated rainwater and with a pH greater than 10. These groups showed high levels of genetic diversity at the habitat level based on the percentage of polymorphic bands (90.32, 82.56%), Nei's gene diversity index (0.262, 0.248), and the Shannon diversity index (0.407, 0.383). Although little is known about the between-habitat genetic differentiation of P. australis on a small spatial scale, our results implied significant genetic differentiation between habitats. Extensive epigenetic diversity within habitats, along with clear differentiation, was found. Specifically, the former habitat (Habitat 1, designated H1) harbored higher levels of genetic and epigenetic diversity than the latter (Habitat 2, designated H2), and population-level diversity was also high. This study represents one of few attempts to predict habitat-based genetic differentiation of reeds on a small scale. These assessments of genetic and epigenetic variation are integral aspects of molecular ecological studies on P. australis. Possible causes for within- and between-habitat genetic and epigenetic variations are discussed.

  14. Implications of long-term culture for mesenchymal stem cells: genetic defects or epigenetic regulation?

    Science.gov (United States)

    Wagner, Wolfgang

    2012-12-20

    Mesenchymal stem cells change dramatically during culture expansion. Long-term culture has been suspected to evoke oncogenic transformation: overall, the genome appears to be relatively stable throughout culture but transient clonal aneuploidies have been observed. Oncogenic transformation does not necessarily entail growth advantage in vitro and, therefore, the available methods - such as karyotypic analysis or genomic profiling - cannot exclude this risk. On the other hand, long-term culture is associated with specific senescence-associated DNA methylation (SA-DNAm) changes, particularly in developmental genes. SA-DNAm changes are highly reproducible and can be used to monitor the state of senescence for quality control. Notably, neither telomere attrition nor SA-DNAm changes occur in pluripotent stem cells, which can evade the 'Hayflick limit'. Long-term culture of mesenchymal stem cells seems to involve a tightly regulated epigenetic program. These epigenetic modifications may counteract dominant clones, which are more prone to transformation.

  15. Epigenetics in plant tissue culture

    NARCIS (Netherlands)

    Smulders, M.J.M.; Klerk, de G.J.M.

    2011-01-01

    Plants produced vegetatively in tissue culture may differ from the plants from which they have been derived. Two major classes of off-types occur: genetic ones and epigenetic ones. This review is about epigenetic aberrations. We discuss recent studies that have uncovered epigenetic modifications at

  16. Epi-genetics modifications induced by a depleted uranium exposure in the zebra fish

    Energy Technology Data Exchange (ETDEWEB)

    Gombeau, K.; Pereira, S.; Adam-Guillermin, C. [IRSN/PRP-ENV/SERIS/LECO (France); Bourdineaud, J.P. [UMR CNRS 5805 EPOC (France); Ravanat, J.L. [INAC/Scib UMR E3 CEA-UJF (France)

    2014-07-01

    The work presented here integrates in the general framework of assessment of effects of chronic exposure to low doses of radionuclides. This evaluation necessarily involves the study of the mechanisms of toxic action at the cellular or subcellular level, in order to better understand the processes of propagation of effects to the level of the populations or ecosystems. As such, the question of the mechanisms underlying the trans-generational effects and the adaptive capacity of organisms is central, both in humans and in animal species. Epigenetic refer to changes in gene function that do not involve changes in DNA sequence, and which are transmitted in a hereditary manner by mitosis or meiosis. The latter plays a key role in these trans-generational effects. Among these changes, DNA-methylation is one of the most studied epigenetic parameters. This work is part of a PhD, included in the European COMET project (Euratom 7. Framework Program), and focuses on epigenetic modifications induced in zebra fish after a chronic exposure to radionuclides. Male and female fishes were exposed to 2 and 20 μg.L{sup -1} of depleted uranium for 24 days. After 7 and 24 days of exposure, brain, gonads, and eyes were collected in order to study changes in DNA methylation. In addition, genotoxicity was measured by the γH2AX assay. The overall changes in DNA methylation were studied by AFLP-MS and HPLC-MS, in order to know if the exposure to depleted uranium changes the global status of DNA methylation. We have found a decrease in the global level of methylation in the eyes of males after 24 days of exposure, the diminution being much more important and significant at the higher concentration of exposure (11.79 ± 3.62 against 52.43 ± 3.01 for controls) This study will be refined by analyzing the methylation of specific regions of the genome, because it represent the sequences of genes involved in major physiological functions and that may be subject to variations in the methylation

  17. Assessment of genetic and epigenetic changes in virus-free garlic (Allium sativum L.) plants obtained by meristem culture followed by in vitro propagation.

    Science.gov (United States)

    Gimenez, Magalí Diana; Yañez-Santos, Anahí Mara; Paz, Rosalía Cristina; Quiroga, Mariana Paola; Marfil, Carlos Federico; Conci, Vilma Cecilia; García-Lampasona, Sandra Claudia

    2016-01-01

    This is the first report assessing epigenetic variation in garlic. High genetic and epigenetic polymorphism during in vitro culture was detected.Sequencing of MSAP fragments revealed homology with ESTs. Garlic (Allium sativum) is a worldwide crop of economic importance susceptible to viral infections that can cause significant yield losses. Meristem tissue culture is the most employed method to sanitize elite cultivars.Often the virus-free garlic plants obtained are multiplied in vitro (micro propagation). However, it was reported that micro-propagation frequently produces somaclonal variation at the phenotypic level, which is an undesirable trait when breeders are seeking to maintain varietal stability. We employed amplification fragment length polymorphism and methylation sensitive amplified polymorphism (MSAP) methodologies to assess genetic and epigenetic modifications in two culture systems: virus-free plants obtained by meristem culture followed by in vitro multiplication and field culture. Our results suggest that garlic exhibits genetic and epigenetic polymorphism under field growing conditions. However, during in vitro culture system both kinds of polymorphisms intensify indicating that this system induces somaclonal variation. Furthermore, while genetic changes accumulated along the time of in vitro culture, epigenetic polymorphism reached the major variation at 6 months and then stabilize, being demethylation and CG methylation the principal conversions.Cloning and sequencing differentially methylated MSAP fragments allowed us to identify coding and unknown sequences of A. sativum, including sequences belonging to LTR Gypsy retrotransposons. Together, our results highlight that main changes occur in the initial 6 months of micro propagation. For the best of our knowledge, this is the first report on epigenetic assessment in garlic.

  18. Advancement of Phenotype Transformation of Cancer-associated Fibroblasts: 
from Genetic Alterations to Epigenetic Modification

    Directory of Open Access Journals (Sweden)

    Dali CHEN

    2015-02-01

    Full Text Available In the field of human cancer research, even though the vast majority attentions were paid to tumor cells as “the seeds”, the roles of tumor microenvironments as “the soil” are gradually explored in recent years. As a dominant compartment of tumor microenvironments, cancer-associated fibroblasts (CAFs were discovered to correlated with tumorigenesis, tumor progression and prognosis. And the exploration of the mechanisms of CAF phenotype transformation would conducive to the further understand of the CAFs function in human cancers. As we known that CAFs have four main origins, including epithelial cells, endothelial cells, mesenchymal stem cells (MSCs and local mesenchymal cells. However, researchers found that all these origins finally conduct similiar phenotypes from intrinsic to extrinsic ones. Thus, what and how a mechanism can conduct the phenotype transformation of CAFs with different origins? Two viewpoints are proposed to try to answer the quetsion, involving genetic alterations and epigenetic modifications. This review will systematically summarize the advancement of mechanisms of CAF phenotype transformations in the aspect of genentic and epigenetic modifications.

  19. Genetic and Epigenetic Tumor Suppressor Gene Silencing are Distinct Molecular Phenotypes Driven by Growth Promoting Mutations in Non small Cell Lung Cancer

    International Nuclear Information System (INIS)

    Marsit, C. J.; Kelsey, K. T.; Houseman, E. A.; Kelsey, K. T.; Houseman, E. A.; Nelson, H. H.

    2008-01-01

    Both genetic and epigenetic alterations characterize human non small cell lung cancer (NSCLC), but the biological processes that create or select these alterations remain incompletely investigated. Our hypothesis posits that a roughly reciprocal relationship between the propensity for promoter hyper methylation and a propensity for genetic deletion leads to distinct molecular phenotypes of lung cancer. To test this hypothesis, we examined promoter hyper methylation of 17 tumor suppressor genes, as a marker of epigenetic alteration propensity, and deletion events at the 3p21 region, as a marker of genetic alteration. To model the complex biology between these somatic alterations, we utilized an item response theory model. We demonstrated that tumors exhibiting LOH at greater than 30% of informative alleles in the 3p21 region have a significantly reduced propensity for hyper methylation. At the same time, tumors with activating KRAS mutations showed a significantly increased propensity for hyper methylation of the loci examined, a result similar to what has been observed in colon cancer. These data suggest that NSCLCs have distinct epigenetic or genetic alteration phenotypes acting upon tumor suppressor genes and that mutation of oncogenic growth promoting genes, such as KRAS, is associated with the epigenetic phenotype.

  20. Genetic and Epigenetic Tumor Suppressor Gene Silencing Are Distinct Molecular Phenotypes Driven by Growth Promoting Mutations in Nonsmall Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Carmen J. Marsit

    2008-01-01

    Full Text Available Both genetic and epigenetic alterations characterize human nonsmall cell lung cancer (NSCLC, but the biological processes that create or select these alterations remain incompletely investigated. Our hypothesis posits that a roughly reciprocal relationship between the propensity for promoter hypermethylation and a propensity for genetic deletion leads to distinct molecular phenotypes of lung cancer. To test this hypothesis, we examined promoter hypermethylation of 17 tumor suppressor genes, as a marker of epigenetic alteration propensity, and deletion events at the 3p21 region, as a marker of genetic alteration. To model the complex biology between these somatic alterations, we utilized an item response theory model. We demonstrated that tumors exhibiting LOH at greater than 30% of informative alleles in the 3p21 region have a significantly reduced propensity for hypermethylation. At the same time, tumors with activating KRAS mutations showed a significantly increased propensity for hypermethylation of the loci examined, a result similar to what has been observed in colon cancer. These data suggest that NSCLCs have distinct epigenetic or genetic alteration phenotypes acting upon tumor suppressor genes and that mutation of oncogenic growth promoting genes, such as KRAS, is associated with the epigenetic phenotype.

  1. Genetic and Epigenetic Alterations of Brassica nigra Introgression Lines from Somatic Hybridization: A Resource for Cauliflower Improvement.

    Science.gov (United States)

    Wang, Gui-Xiang; Lv, Jing; Zhang, Jie; Han, Shuo; Zong, Mei; Guo, Ning; Zeng, Xing-Ying; Zhang, Yue-Yun; Wang, You-Ping; Liu, Fan

    2016-01-01

    Broad phenotypic variations were obtained previously in derivatives from the asymmetric somatic hybridization of cauliflower "Korso" (Brassica oleracea var. botrytis, 2n = 18, CC genome) and black mustard "G1/1" (Brassica nigra, 2n = 16, BB genome). However, the mechanisms underlying these variations were unknown. In this study, 28 putative introgression lines (ILs) were pre-selected according to a series of morphological (leaf shape and color, plant height and branching, curd features, and flower traits) and physiological (black rot/club root resistance) characters. Multi-color fluorescence in situ hybridization revealed that these plants contained 18 chromosomes derived from "Korso." Molecular marker (65 simple sequence repeats and 77 amplified fragment length polymorphisms) analysis identified the presence of "G1/1" DNA segments (average 7.5%). Additionally, DNA profiling revealed many genetic and epigenetic differences among the ILs, including sequence alterations, deletions, and variation in patterns of cytosine methylation. The frequency of fragments lost (5.1%) was higher than presence of novel bands (1.4%), and the presence of fragments specific to Brassica carinata (BBCC 2n = 34) were common (average 15.5%). Methylation-sensitive amplified polymorphism analysis indicated that methylation changes were common and that hypermethylation (12.4%) was more frequent than hypomethylation (4.8%). Our results suggested that asymmetric somatic hybridization and alien DNA introgression induced genetic and epigenetic alterations. Thus, these ILs represent an important, novel germplasm resource for cauliflower improvement that can be mined for diverse traits of interest to breeders and researchers.

  2. Genetic and epigenetic alterations of Brassica nigra introgression lines from somatic hybridization: a resource for cauliflower improvement

    Directory of Open Access Journals (Sweden)

    Guixiang Wang

    2016-08-01

    Full Text Available Broad phenotypic variations were obtained previously in derivatives from the asymmetric somatic hybridization of cauliflower ‘Korso’ (Brassica oleracea var. botrytis, 2n = 18, CC genome and black mustard ‘G1/1’ (Brassica nigra, 2n = 16, BB genome. However, the mechanisms underlying these variations were unknown. In this study, 28 putative introgression lines (ILs were pre-selected according to a series of morphological (leaf shape and color, plant height and branching, curd features, and flower traits and physiological (black rot/club root resistance characters. Multi-color fluorescence in situ hybridization revealed that these plants contained 18 chromosomes derived from ‘Korso’. Molecular marker (65 simple sequence repeats and 77 amplified fragment length polymorphisms analysis identified the presence of ‘G1/1’ DNA segments (average 7.5%. Additionally, DNA profiling revealed many genetic and epigenetic differences among the ILs, including sequence alterations, deletions, and variation in patterns of cytosine methylation. The frequency of fragments lost (5.1% was significantly higher than presence of novel bands (1.4%, and the presence of fragments specific to B. carinata (BBCC 2n = 34 were common (average 15.5%. Methylation-sensitive amplified polymorphism analysis indicated that methylation changes were common and that hypermethylation (12.4% was more frequent than hypomethylation (4.8%. Our results suggested that asymmetric somatic hybridization and alien DNA introgression induced genetic and epigenetic alterations. Thus, these ILs represent an important, novel germplasm resource for cauliflower improvement that can be mined for diverse traits of interest to breeders and researchers.

  3. What Is Direct-to-Consumer Genetic Testing?

    Science.gov (United States)

    ... consumer genetic testing. Additional information about direct-to-consumer marketing of genetic tests and related research questions are ... for Links Data Files & API Site Map Subscribe Customer Support USA.gov Copyright Privacy Accessibility FOIA Viewers & ...

  4. Comparative analyses of genetic/epigenetic diversities and structures in a wild barley species (Hordeum brevisubulatum) using MSAP, SSAP and AFLP.

    Science.gov (United States)

    Shan, X H; Li, Y D; Liu, X M; Wu, Y; Zhang, M Z; Guo, W L; Liu, B; Yuan, Y P

    2012-08-17

    We analyzed genetic diversity and population genetic structure of four artificial populations of wild barley (Hordeum brevisubulatum); 96 plants collected from the Songnen Prairie in northeastern China were analyzed using amplified fragment length polymorphism (AFLP), specific-sequence amplified polymorphism (SSAP) and methylation-sensitive amplified polymorphism (MSAP) markers. Indices of (epi-)genetic diversity, (epi-)genetic distance, gene flow, genotype frequency, cluster analysis, PCA analysis and AMOVA analysis generated from MSAP, AFLP and SSAP markers had the same trend. We found a high level of correlation in the artificial populations between MSAP, SSAP and AFLP markers by the Mantel test (r > 0.8). This is incongruent with previous findings showing that there is virtually no correlation between DNA methylation polymorphism and classical genetic variation; the high level of genetic polymorphism could be a result of epigenetic regulation. We compared our results with data from natural populations. The population diversity of the artificial populations was lower. However, different from what was found using AFLP and SSAP, based on MSAP results the methylation polymorphism of the artificial populations was not significantly reduced. This leads us to suggest that the DNA methylation pattern change in H. brevisubulatum populations is not only related to DNA sequence variation, but is also regulated by other controlling systems.

  5. Epigenetic considerations in aquaculture

    Directory of Open Access Journals (Sweden)

    Mackenzie R. Gavery

    2017-12-01

    Full Text Available Epigenetics has attracted considerable attention with respect to its potential value in many areas of agricultural production, particularly under conditions where the environment can be manipulated or natural variation exists. Here we introduce key concepts and definitions of epigenetic mechanisms, including DNA methylation, histone modifications and non-coding RNA, review the current understanding of epigenetics in both fish and shellfish, and propose key areas of aquaculture where epigenetics could be applied. The first key area is environmental manipulation, where the intention is to induce an ‘epigenetic memory’ either within or between generations to produce a desired phenotype. The second key area is epigenetic selection, which, alone or combined with genetic selection, may increase the reliability of producing animals with desired phenotypes. Based on aspects of life history and husbandry practices in aquaculture species, the application of epigenetic knowledge could significantly affect the productivity and sustainability of aquaculture practices. Conversely, clarifying the role of epigenetic mechanisms in aquaculture species may upend traditional assumptions about selection practices. Ultimately, there are still many unanswered questions regarding how epigenetic mechanisms might be leveraged in aquaculture.

  6. Epigenetic regulation of the transcription factor Foxa2 directs differential elafin expression in melanocytes and melanoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Kyung Sook [Therapeutic Antibody Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806 (Korea, Republic of); Jo, Ji Yoon; Kim, Su Jin [Therapeutic Antibody Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806 (Korea, Republic of); Department of Functional Genomics, University of Science and Technology, Daejeon 305-333 (Korea, Republic of); Lee, Yangsoon [Therapeutic Antibody Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806 (Korea, Republic of); Bae, Jong Hwan [NeoPharm Co. Ltd., Daejeon 305-510 (Korea, Republic of); Chung, Young-Hwa [Department of Cogno-Mechatronics Engineering, BK21 Nanofusion Technology Team, Pusan National University, Busan 609-736 (Korea, Republic of); Koh, Sang Seok, E-mail: sskoh@kribb.re.kr [Therapeutic Antibody Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806 (Korea, Republic of); Department of Functional Genomics, University of Science and Technology, Daejeon 305-333 (Korea, Republic of)

    2011-04-29

    Highlights: {yields} Elafin expression is epigenetically silenced in human melanoma cells. {yields} Foxa2 expression in melanoma cells is silenced by promoter hypermethylation. {yields} Foxa2 directs activation of the elafin promoter in vivo. {yields} Foxa2 expression induces apoptosis of melanoma cells via elafin re-expression. -- Abstract: Elafin, a serine protease inhibitor, induces the intrinsic apoptotic pathway in human melanoma cells, where its expression is transcriptionally silenced. However, it remains unknown how the elafin gene is repressed in melanoma cells. We here demonstrate that elafin expression is modulated via epigenetically regulated expression of the transcription factor Foxa2. Treatment of melanoma cells with a DNA methyltransferase inhibitor induced elafin expression, which was specifically responsible for reduced proliferation and increased apoptosis. Suppression of Foxa2 transcription, mediated by DNA hypermethylation in its promoter region, was released in melanoma cells upon treatment with the demethylating agent. Luciferase reporter assays indicated that the Foxa2 binding site in the elafin promoter was critical for the activation of the promoter. Chromatin immunoprecipitation assays further showed that Foxa2 bound to the elafin promoter in vivo. Analyses of melanoma cells with varied levels of Foxa2 revealed a correlated expression between Foxa2 and elafin and the ability of Foxa2 to induce apoptosis. Our results collectively suggest that, in melanoma cells, Foxa2 expression is silenced and therefore elafin is maintained unexpressed to facilitate cell proliferation in the disease melanoma.

  7. Predicting cell types and genetic variations contributing to disease by combining GWAS and epigenetic data.

    Directory of Open Access Journals (Sweden)

    Anna Gerasimova

    Full Text Available Genome-wide association studies (GWASs identify single nucleotide polymorphisms (SNPs that are enriched in individuals suffering from a given disease. Most disease-associated SNPs fall into non-coding regions, so that it is not straightforward to infer phenotype or function; moreover, many SNPs are in tight genetic linkage, so that a SNP identified as associated with a particular disease may not itself be causal, but rather signify the presence of a linked SNP that is functionally relevant to disease pathogenesis. Here, we present an analysis method that takes advantage of the recent rapid accumulation of epigenomics data to address these problems for some SNPs. Using asthma as a prototypic example; we show that non-coding disease-associated SNPs are enriched in genomic regions that function as regulators of transcription, such as enhancers and promoters. Identifying enhancers based on the presence of the histone modification marks such as H3K4me1 in different cell types, we show that the location of enhancers is highly cell-type specific. We use these findings to predict which SNPs are likely to be directly contributing to disease based on their presence in regulatory regions, and in which cell types their effect is expected to be detectable. Moreover, we can also predict which cell types contribute to a disease based on overlap of the disease-associated SNPs with the locations of enhancers present in a given cell type. Finally, we suggest that it will be possible to re-analyze GWAS studies with much higher power by limiting the SNPs considered to those in coding or regulatory regions of cell types relevant to a given disease.

  8. Investigating the potential role of genetic and epigenetic variation of DNA methyltransferase genes in hyperplastic polyposis syndrome.

    Directory of Open Access Journals (Sweden)

    Musa Drini

    2011-02-01

    Full Text Available Hyperplastic Polyposis Syndrome (HPS is a condition associated with multiple serrated polyps, and an increased risk of colorectal cancer (CRC. At least half of CRCs arising in HPS show a CpG island methylator phenotype (CIMP, potentially linked to aberrant DNA methyltransferase (DNMT activity. CIMP is associated with methylation of tumor suppressor genes including regulators of DNA mismatch repair (such as MLH1, MGMT, and negative regulators of Wnt signaling (such as WIF1. In this study, we investigated the potential for interaction of genetic and epigenetic variation in DNMT genes, in the aetiology of HPS.We utilized high resolution melting (HRM analysis to screen 45 cases with HPS for novel sequence variants in DNMT1, DNMT3A, DNMT3B, and DNMT3L. 21 polyps from 13 patients were screened for BRAF and KRAS mutations, with assessment of promoter methylation in the DNMT1, DNMT3A, DNMT3B, DNMT3L MLH1, MGMT, and WIF1 gene promoters.No pathologic germline mutations were observed in any DNA-methyltransferase gene. However, the T allele of rs62106244 (intron 10 of DNMT1 gene was over-represented in cases with HPS (p<0.01 compared with population controls. The DNMT1, DNMT3A and DNMT3B promoters were unmethylated in all instances. Interestingly, the DNMT3L promoter showed low levels of methylation in polyps and normal colonic mucosa relative to matched disease free cells with methylation level negatively correlated to expression level in normal colonic tissue. DNMT3L promoter hypomethylation was more often found in polyps harbouring KRAS mutations (p = 0.0053. BRAF mutations were common (11 out of 21 polyps, whilst KRAS mutations were identified in 4 of 21 polyps.Genetic or epigenetic alterations in DNMT genes do not appear to be associated with HPS, but further investigation of genetic variation at rs62106244 is justified given the high frequency of the minor allele in this case series.

  9. Genetic and Epigenetic Changes in Oilseed Rape (Brassica napus L.) Extracted from Intergeneric Allopolyploid and Additions with Orychophragmus.

    Science.gov (United States)

    Gautam, Mayank; Dang, Yanwei; Ge, Xianhong; Shao, Yujiao; Li, Zaiyun

    2016-01-01

    Allopolyploidization with the merger of the genomes from different species has been shown to be associated with genetic and epigenetic changes. But the maintenance of such alterations related to one parental species after the genome is extracted from the allopolyploid remains to be detected. In this study, the genome of Brassica napus L. (2n = 38, genomes AACC) was extracted from its intergeneric allohexaploid (2n = 62, genomes AACCOO) with another crucifer Orychophragmus violaceus (2n = 24, genome OO), by backcrossing and development of alien addition lines. B. napus-type plants identified in the self-pollinated progenies of nine monosomic additions were analyzed by the methods of amplified fragment length polymorphism, sequence-specific amplified polymorphism, and methylation-sensitive amplified polymorphism. They showed modifications to certain extents in genomic components (loss and gain of DNA segments and transposons, introgression of alien DNA segments) and DNA methylation, compared with B. napus donor. The significant differences in the changes between the B. napus types extracted from these additions likely resulted from the different effects of individual alien chromosomes. Particularly, the additions which harbored the O. violaceus chromosome carrying dominant rRNA genes over those of B. napus tended to result in the development of plants which showed fewer changes, suggesting a role of the expression levels of alien rRNA genes in genomic stability. These results provided new cues for the genetic alterations in one parental genome that are maintained even after the genome becomes independent.

  10. Genetic and epigenetic changes in oilseed rape (Brassica napus L. extracted from intergeneric allopolyploid and additions with Orychophragmus

    Directory of Open Access Journals (Sweden)

    Mayank eGautam

    2016-04-01

    Full Text Available ABSTRACT Allopolyploidization with the merger of the genomes from different species has been shown to be associated with genetic and epigenetic changes. But the maintenance of such alterations related to one parental species after the genome is extracted from the allopolyploid remains to be detected. In this study, the genome of Brassica napus L. (2n=38, genomes AACC was extracted from its intergeneric allohexaploid (2n=62, genomes AACCOO with another crucifer Orychophragmus violaceus (2n=24, genome OO, by backcrossing and development of alien addition lines. B. napus-type plants identified in the self-pollinated progenies of nine monosomic additions were analyzed by the methods of amplified fragment length polymorphism (AFLP, sequence-specific amplified polymorphism (SSAP, and methylation-sensitive amplified polymorphism (MSAP. They showed modifications to certain extents in genomic components (loss and gain of DNA segments and transposons, introgression of alien DNA segments and DNA methylation, compared with B. napus donor. The significant differences in the changes between the B. napus types extracted from these additions likely resulted from the different effects of individual alien chromosomes. Particularly, the additions which harbored the O. violaceus chromosome carrying dominant rRNA genes over those of B. napus tended to result in the development of plants which showed fewer changes, suggesting a role of the expression levels of alien rRNA genes in genomic stability. These results provided new cues for the genetic alterations in one parental genome that are maintained even after the genome becomes independent.

  11. Genetic and Epigenetic Approaches for the Possible Detection of Adulteration and Auto-Adulteration in Saffron (Crocus sativus L. Spice

    Directory of Open Access Journals (Sweden)

    Giovanna Soffritti

    2016-03-01

    Full Text Available Saffron (Crocus sativus L. is very expensive and, because of this, often subject to adulteration. Modern genetic fingerprinting techniques are an alternative low cost technology to the existing chemical techniques, which are used to control the purity of food products. Buddleja officinalis Maxim, Gardenia jasminoides Ellis, Curcuma longa L., Carthamus tinctorius L. and Calendula officinalis L. are among the most frequently-used adulterants in saffron spice. Three commercial kits were compared concerning the ability to recover PCR-grade DNA from saffron, truly adulterated samples and possible adulterants, with a clear difference among them, mainly with the processed samples. Only one of the three kits was able to obtain amplifiable DNA from almost all of the samples, with the exception of extracts. On the recovered DNA, new markers were developed based on the sequence of the plastid genes matK and rbcL. These primers, mainly those developed on matK, were able to recognize saffron and the adulterant species and also in mixtures with very low percentages of adulterant. Finally, considering that the addition of different parts of saffron flowers is one of the most widespread adulterations, by analyzing the DNA of the different parts of the flower (styles, stamens and tepals at the genetic and epigenetic level, we succeeded in finding differences between the three tissues that can be further evaluated for a possible detection of the kind of fraud.

  12. Determination of epigenetic inheritance, genetic inheritance, and estimation of genome DNA methylation in a full-sib family of Cupressus sempervirens L.

    Science.gov (United States)

    Avramidou, Evangelia V; Doulis, Andreas G; Aravanopoulos, Filippos A

    2015-05-15

    Genetic inheritance and epigenetic inheritance are significant determinants of plant evolution, adaptation and plasticity. We studied inheritance of restriction site polymorphisms by the f-AFLP method and epigenetic DNA cytosine methylation inheritance by the f-MSAP technique. The study involved parents and 190 progeny of a Cupressus sempervirens L. full-sib family. Results from AFLP genetic data revealed that 71.8% of the fragments studied are under Mendelian genetic control, whereas faithful Mendelian inheritance for the MSAP fragments was low (4.29%). Further, MSAP fragment analysis showed that total methylation presented a mean of 28.2%, which was higher than the midparent value, while maternal inheritance was higher (5.65%) than paternal (3.01%). Interestingly de novo methylation in the progeny was high (19.65%) compared to parental methylation. Genetic and epigenetic distances for parents and offspring were not correlated (R(2)=0.0005). Furthermore, we studied correlation of total relative methylation and CG methylation with growth (height, diameter). We found CG/CNG methylation (N: A, C, T) to be positively correlated with height and diameter, while total relative methylation and CG methylation were positively correlated with height. Results are discussed in light of further research needed and of their potential application in breeding. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. A model for genetic and epigenetic regulatory networks identifies rare pathways for transcription factor induced pluripotency

    Science.gov (United States)

    Artyomov, Maxim; Meissner, Alex; Chakraborty, Arup

    2010-03-01

    Most cells in an organism have the same DNA. Yet, different cell types express different proteins and carry out different functions. This is because of epigenetic differences; i.e., DNA in different cell types is packaged distinctly, making it hard to express certain genes while facilitating the expression of others. During development, upon receipt of appropriate cues, pluripotent embryonic stem cells differentiate into diverse cell types that make up the organism (e.g., a human). There has long been an effort to make this process go backward -- i.e., reprogram a differentiated cell (e.g., a skin cell) to pluripotent status. Recently, this has been achieved by transfecting certain transcription factors into differentiated cells. This method does not use embryonic material and promises the development of patient-specific regenerative medicine, but it is inefficient. The mechanisms that make reprogramming rare, or even possible, are poorly understood. We have developed the first computational model of transcription factor-induced reprogramming. Results obtained from the model are consistent with diverse observations, and identify the rare pathways that allow reprogramming to occur. If validated, our model could be further developed to design optimal strategies for reprogramming and shed light on basic questions in biology.

  14. Dynamic EBF1 occupancy directs sequential epigenetic and transcriptional events in B-cell programming.

    Science.gov (United States)

    Li, Rui; Cauchy, Pierre; Ramamoorthy, Senthilkumar; Boller, Sören; Chavez, Lukas; Grosschedl, Rudolf

    2018-01-15

    B-cell fate determination requires the action of transcription factors that operate in a regulatory network to activate B-lineage genes and repress lineage-inappropriate genes. However, the dynamics and hierarchy of events in B-cell programming remain obscure. To uncouple the dynamics of transcription factor expression from functional consequences, we generated induction systems in developmentally arrested Ebf1 -/- pre-pro-B cells to allow precise experimental control of EBF1 expression in the genomic context of progenitor cells. Consistent with the described role of EBF1 as a pioneer transcription factor, we show in a time-resolved analysis that EBF1 occupancy coincides with EBF1 expression and precedes the formation of chromatin accessibility. We observed dynamic patterns of EBF1 target gene expression and sequential up-regulation of transcription factors that expand the regulatory network at the pro-B-cell stage. A continuous EBF1 function was found to be required for Cd79a promoter activity and for the maintenance of an accessible chromatin domain that is permissive for binding of other transcription factors. Notably, transient EBF1 occupancy was detected at lineage-inappropriate genes prior to their silencing in pro-B cells. Thus, persistent and transient functions of EBF1 allow for an ordered sequence of epigenetic and transcriptional events in B-cell programming. © 2018 Li et al.; Published by Cold Spring Harbor Laboratory Press.

  15. Eating Disorders and Epigenetics.

    Science.gov (United States)

    Thaler, Lea; Steiger, Howard

    2017-01-01

    Eating disorders (EDs) are characterized by intense preoccupation with shape and weight and maladaptive eating practices. The complex of symptoms that characterize EDs often arise through the activation of latent genetic potentials by environmental exposures, and epigenetic mechanisms are believed to link environmental exposures to gene expression. This chapter provides an overview of genetic factors acting in the etiology of EDs. It then provides a background to the hypothesis that epigenetic mechanisms link stresses such as obstetric complications and childhood abuse as well as effects of malnutrition to eating disorders (EDs). The chapter then summarizes the emerging body of literature on epigenetics and EDs-mainly studies on DNA methylation in samples of anorexia and bulimia. The available evidence base suggests that an epigenetically informed perspective contributes in valuable ways to the understanding of why people develop EDs.

  16. Epigenetics in natural animal populations.

    Science.gov (United States)

    Hu, J; Barrett, R D H

    2017-09-01

    Phenotypic plasticity is an important mechanism for populations to buffer themselves from environmental change. While it has long been appreciated that natural populations possess genetic variation in the extent of plasticity, a surge of recent evidence suggests that epigenetic variation could also play an important role in shaping phenotypic responses. Compared with genetic variation, epigenetic variation is more likely to have higher spontaneous rates of mutation and a more sensitive reaction to environmental inputs. In our review, we first provide an overview of recent studies on epigenetically encoded thermal plasticity in animals to illustrate environmentally-mediated epigenetic effects within and across generations. Second, we discuss the role of epigenetic effects during adaptation by exploring population epigenetics in natural animal populations. Finally, we evaluate the evolutionary potential of epigenetic variation depending on its autonomy from genetic variation and its transgenerational stability. Although many of the causal links between epigenetic variation and phenotypic plasticity remain elusive, new data has explored the role of epigenetic variation in facilitating evolution in natural populations. This recent progress in ecological epigenetics will be helpful for generating predictive models of the capacity of organisms to adapt to changing climates. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

  17. Genetic, nongenetic and epigenetic risk determinants in developmental programming of type 2 diabetes

    DEFF Research Database (Denmark)

    Vaag, Allan; Brøns, Charlotte; Gillberg, Linn

    2014-01-01

    Low birthweight (LBW) individuals and offspring of women with gestational diabetes mellitus (GDM) exhibit increased risk of developing type 2 diabetes (T2D) and associated cardiometabolic traits in adulthood, which for both groups may be mediated by adverse events and developmental changes in fetal...... factors. Indeed, it has been shown that genetic changes influencing risk of diabetes may also be associated with reduced fetal growth as a result of reduced insulin secretion and/or action. Similarly, increased risk of T2D among offspring could be explained by T2D susceptibility genes shared between...... life. T2D is a multifactorial disease occurring as a result of complicated interplay between genetic and both prenatal and postnatal nongenetic factors, and it remains unknown to what extent the increased risk of T2D associated with LBW or GDM in the mother may be due to, or confounded by, genetic...

  18. Strategies for Integrated Analysis of Genetic, Epigenetic, and Gene Expression Variation in Cancer

    DEFF Research Database (Denmark)

    Thingholm, Louise B; Andersen, Lars; Makalic, Enes

    2016-01-01

    The development and progression of cancer, a collection of diseases with complex genetic architectures, is facilitated by the interplay of multiple etiological factors. This complexity challenges the traditional single-platform study design and calls for an integrated approach to data analysis...... to integration strategies used for analyzing genetic risk factors for cancer. We critically examine the ability of these strategies to handle the complexity of the human genome and also accommodate information about the biological and functional interactions between the elements that have been measured...

  19. Strategies for Integrated Analysis of Genetic, Epigenetic, and Gene Expression Variation in Cancer: Addressing the Challenges

    DEFF Research Database (Denmark)

    Thingholm, Louise Bruun; Andersen, Lars; Makalic, Enes

    2016-01-01

    to integration strategies used for analyzing genetic risk factors for cancer. We critically examine the ability of these strategies to handle the complexity of the human genome and also accommodate information about the biological and functional interactions between the elements that have been measured......The development and progression of cancer, a collection of diseases with complex genetic architectures, is facilitated by the interplay of multiple etiological factors. This complexity challenges the traditional single-platform study design and calls for an integrated approach to data analysis...

  20. Obesity: epigenetic aspects.

    Science.gov (United States)

    Kaushik, Prashant; Anderson, James T

    2016-06-01

    Epigenetics, defined as inheritable and reversible phenomena that affect gene expression without altering the underlying base pair sequence has been shown to play an important role in the etiopathogenesis of obesity. Obesity is associated with extensive gene expression changes in tissues throughout the body. Epigenetics is emerging as perhaps the most important mechanism through which the lifestyle-choices we make can directly influence the genome. Considerable epidemiological, experimental and clinical data have been amassed showing that the risk of developing disease in later life is dependent on early life conditions, mainly operating within the normative range of developmental exposures. In addition to the 'maternal' interactions, there has been increasing interest in the epigenetic mechanisms through which 'paternal' influences on offspring development can be achieved. Nutrition, among many other environmental factors, is a key player that can induce epigenetic changes not only in the directly exposed organisms but also in subsequent generations through the transgenerational inheritance of epigenetic traits. Overall, significant progress has been made in the field of epigenetics and obesity and the first potential epigenetic markers for obesity that could be detected at birth have been identified. Fortunately, epigenetic phenomena are dynamic and rather quickly reversible with intensive lifestyle changes. This is a very promising and sustainable resolution to the obesity pandemic.

  1. Direct genetic transformation of Hibiscus sabdariffa L.

    African Journals Online (AJOL)

    Administrator

    After 60 days evaluation point, the assessment of the transformation by PCR revealed that H. sabdariffa line tested, carried the nptII gene. Key words: Hibiscus sabdariffa, genetic transformation. INTRODUCTION. Hibiscus sabdariffa is a crop widely cultivated in Sub. Saharan Africa, growing on sandy soils after the harvest.

  2. Cracking anxiety in the mouse : a quantitative (epi)genetic approach

    NARCIS (Netherlands)

    Labots, M.

    2017-01-01

    The aim of this thesis was to improve existing methodologies and apply genetic strategies in order to identify (main-effect, epistatic, multiple and pleiotropic) quantitative trait loci and to decipher functional candidate genes for anxiety-related behavior and baseline blood plasma total

  3. Epigenetic modifications in prostate cancer.

    Science.gov (United States)

    Ngollo, Marjolaine; Dagdemir, Aslihan; Karsli-Ceppioglu, Seher; Judes, Gaelle; Pajon, Amaury; Penault-Llorca, Frederique; Boiteux, Jean-Paul; Bignon, Yves-Jean; Guy, Laurent; Bernard-Gallon, Dominique J

    2014-01-01

    Prostate cancer is the most common cancer in men and the second leading cause of cancer deaths in men in France. Apart from the genetic alterations in prostate cancer, epigenetics modifications are involved in the development and progression of this disease. Epigenetic events are the main cause in gene regulation and the three most epigenetic mechanisms studied include DNA methylation, histone modifications and microRNA expression. In this review, we summarized epigenetic mechanisms in prostate cancer. Epigenetic drugs that inhibit DNA methylation, histone methylation and histone acetylation might be able to reactivate silenced gene expression in prostate cancer. However, further understanding of interactions of these enzymes and their effects on transcription regulation in prostate cancer is needed and has become a priority in biomedical research. In this study, we summed up epigenetic changes with emphasis on pharmacologic epigenetic target agents.

  4. Epigenetic Variation May Compensate for Decreased Genetic Variation with Introductions: A Case Study Using House Sparrows (Passer domesticus on Two Continents

    Directory of Open Access Journals (Sweden)

    Aaron W. Schrey

    2012-01-01

    Full Text Available Epigenetic mechanisms impact several phenotypic traits and may be important for ecology and evolution. The introduced house sparrow (Passer domesticus exhibits extensive phenotypic variation among and within populations. We screened methylation in populations from Kenya and Florida to determine if methylation varied among populations, varied with introduction history (Kenyan invasion <50 years old, Florida invasion ~150 years old, and could potentially compensate for decrease genetic variation with introductions. While recent literature has speculated on the importance of epigenetic effects for biological invasions, this is the first such study among wild vertebrates. Methylation was more frequent in Nairobi, and outlier loci suggest that populations may be differentiated. Methylation diversity was similar between populations, in spite of known lower genetic diversity in Nairobi, which suggests that epigenetic variation may compensate for decreased genetic diversity as a source of phenotypic variation during introduction. Our results suggest that methylation differences may be common among house sparrows, but research is needed to discern whether methylation impacts phenotypic variation.

  5. A DNA microarray-based methylation-sensitive (MS)-AFLP hybridization method for genetic and epigenetic analyses.

    Science.gov (United States)

    Yamamoto, F; Yamamoto, M

    2004-07-01

    We previously developed a PCR-based DNA fingerprinting technique named the Methylation Sensitive (MS)-AFLP method, which permits comparative genome-wide scanning of methylation status with a manageable number of fingerprinting experiments. The technique uses the methylation sensitive restriction enzyme NotI in the context of the existing Amplified Fragment Length Polymorphism (AFLP) method. Here we report the successful conversion of this gel electrophoresis-based DNA fingerprinting technique into a DNA microarray hybridization technique (DNA Microarray MS-AFLP). By performing a total of 30 (15 x 2 reciprocal labeling) DNA Microarray MS-AFLP hybridization experiments on genomic DNA from two breast and three prostate cancer cell lines in all pairwise combinations, and Southern hybridization experiments using more than 100 different probes, we have demonstrated that the DNA Microarray MS-AFLP is a reliable method for genetic and epigenetic analyses. No statistically significant differences were observed in the number of differences between the breast-prostate hybridization experiments and the breast-breast or prostate-prostate comparisons.

  6. Genetic and epigenetic factors at COL2A1 and ABCA4 influence clinical outcome in congenital toxoplasmosis.

    Directory of Open Access Journals (Sweden)

    Sarra E Jamieson

    2008-06-01

    Full Text Available Primary Toxoplasma gondii infection during pregnancy can be transmitted to the fetus. At birth, infected infants may have intracranial calcification, hydrocephalus, and retinochoroiditis, and new ocular lesions can occur at any age after birth. Not all children who acquire infection in utero develop these clinical signs of disease. Whilst severity of disease is influenced by trimester in which infection is acquired by the mother, other factors including genetic predisposition may contribute.In 457 mother-child pairs from Europe, and 149 child/parent trios from North America, we show that ocular and brain disease in congenital toxoplasmosis associate with polymorphisms in ABCA4 encoding ATP-binding cassette transporter, subfamily A, member 4. Polymorphisms at COL2A1 encoding type II collagen associate only with ocular disease. Both loci showed unusual inheritance patterns for the disease allele when comparing outcomes in heterozygous affected children with outcomes in affected children of heterozygous mothers. Modeling suggested either an effect of mother's genotype, or parent-of-origin effects. Experimental studies showed that both ABCA4 and COL2A1 show isoform-specific epigenetic modifications consistent with imprinting.These associations between clinical outcomes of congenital toxoplasmosis and polymorphisms at ABCA4 and COL2A1 provide novel insight into the molecular pathways that can be affected by congenital infection with this parasite.

  7. Genetic and Epigenetic Factors at COL2A1 and ABCA4 Influence Clinical Outcome in Congenital Toxoplasmosis

    Science.gov (United States)

    Jamieson, Sarra E.; de Roubaix, Lee-Anne; Cortina-Borja, Mario; Tan, Hooi Kuan; Mui, Ernest J.; Cordell, Heather J.; Kirisits, Michael J.; Miller, E. Nancy; Peacock, Christopher S.; Hargrave, Aubrey C.; Coyne, Jessica J.; Boyer, Kenneth; Bessieres, Marie-Hélène; Buffolano, Wilma; Ferret, Nicole; Franck, Jacqueline; Kieffer, François; Meier, Paul; Nowakowska, Dorota E.; Paul, Malgorzata; Peyron, François; Stray-Pedersen, Babill; Prusa, Andrea-Romana; Thulliez, Philippe; Wallon, Martine; Petersen, Eskild; McLeod, Rima; Gilbert, Ruth E.; Blackwell, Jenefer M.

    2008-01-01

    Background Primary Toxoplasma gondii infection during pregnancy can be transmitted to the fetus. At birth, infected infants may have intracranial calcification, hydrocephalus, and retinochoroiditis, and new ocular lesions can occur at any age after birth. Not all children who acquire infection in utero develop these clinical signs of disease. Whilst severity of disease is influenced by trimester in which infection is acquired by the mother, other factors including genetic predisposition may contribute. Methods and Findings In 457 mother-child pairs from Europe, and 149 child/parent trios from North America, we show that ocular and brain disease in congenital toxoplasmosis associate with polymorphisms in ABCA4 encoding ATP-binding cassette transporter, subfamily A, member 4. Polymorphisms at COL2A1 encoding type II collagen associate only with ocular disease. Both loci showed unusual inheritance patterns for the disease allele when comparing outcomes in heterozygous affected children with outcomes in affected children of heterozygous mothers. Modeling suggested either an effect of mother's genotype, or parent-of-origin effects. Experimental studies showed that both ABCA4 and COL2A1 show isoform-specific epigenetic modifications consistent with imprinting. Conclusions These associations between clinical outcomes of congenital toxoplasmosis and polymorphisms at ABCA4 and COL2A1 provide novel insight into the molecular pathways that can be affected by congenital infection with this parasite. PMID:18523590

  8. An integrative multi-dimensional genetic and epigenetic strategy to identify aberrant genes and pathways in cancer

    Directory of Open Access Journals (Sweden)

    Lockwood William W

    2010-05-01

    Full Text Available Abstract Background Genomics has substantially changed our approach to cancer research. Gene expression profiling, for example, has been utilized to delineate subtypes of cancer, and facilitated derivation of predictive and prognostic signatures. The emergence of technologies for the high resolution and genome-wide description of genetic and epigenetic features has enabled the identification of a multitude of causal DNA events in tumors. This has afforded the potential for large scale integration of genome and transcriptome data generated from a variety of technology platforms to acquire a better understanding of cancer. Results Here we show how multi-dimensional genomics data analysis would enable the deciphering of mechanisms that disrupt regulatory/signaling cascades and downstream effects. Since not all gene expression changes observed in a tumor are causal to cancer development, we demonstrate an approach based on multiple concerted disruption (MCD analysis of genes that facilitates the rational deduction of aberrant genes and pathways, which otherwise would be overlooked in single genomic dimension investigations. Conclusions Notably, this is the first comprehensive study of breast cancer cells by parallel integrative genome wide analyses of DNA copy number, LOH, and DNA methylation status to interpret changes in gene expression pattern. Our findings demonstrate the power of a multi-dimensional approach to elucidate events which would escape conventional single dimensional analysis and as such, reduce the cohort sample size for cancer gene discovery.

  9. A Hypomethylated population of Brassica rapa for forward and reverse Epi-genetics

    Directory of Open Access Journals (Sweden)

    Amoah Stephen

    2012-10-01

    Full Text Available Abstract Background Epigenetic marks superimposed on the DNA sequence of eukaryote chromosomes provide agility and plasticity in terms of modulating gene expression, ontology, and response to the environment. Modulating the methylation status of cytosine can generate epialleles, which have been detected and characterised at specific loci in several plant systems, and have the potential to generate novel and relatively stable phenotypes. There have been no systematic attempts to explore and utilise epiallelic variation, and so extend the range of phenotypes available for selection in crop improvement. We developed an approach for generating novel epialleles by perturbation of the DNA methylation status. 5- Azacytidine (5-AzaC provides selective targeting of 5mCG, which in plants is associated with exonic DNA. Targeted chemical intervention using 5-AzaC has advantages over transgenic or mutant modulation of methyltransferases, allowing stochastic generation of epialleles across the genome. Results We demonstrate the potential of stochastic chemically-induced hypomethylation to generate novel and valuable variation for crop improvement. Systematic analysis of dose–response to 5-AzaC in B. rapa guided generation of a selfed stochastically hypomethylated population, used for forward screening of several agronomic traits. Dose–response was sigmoidal for several traits, similar to that observed for chemical mutagens such as EMS. We demonstrated transgenerational inheritance of some phenotypes. BraRoAZ is a unique hypomethylated population of 1000 E2 sib lines. When compared to untreated controls, 5-Aza C-treated lines exhibited reduced immuno-staining of 5mC on pachytene chromosomes, and Methylation Sensitive Amplified Polymorphism (MSAP profiles that were both divergent and more variable. There was coincident phenotypic variation among these lines for a range of seed yield and composition traits, including increased seed protein content and

  10. Stress, Epigenetics, and Alcoholism

    Science.gov (United States)

    Moonat, Sachin; Pandey, Subhash C.

    2012-01-01

    Acute and chronic stressors have been associated with alterations in mood and increased anxiety that may eventually result in the development of stress-related psychiatric disorders. Stress and associated disorders, including anxiety, are key factors in the development of alcoholism because alcohol consumption can temporarily reduce the drinker’s dysphoria. One molecule that may help mediate the relationship between stress and alcohol consumption is brain-derived neurotrophic factor (BDNF), a protein that regulates the structure and function of the sites where two nerve cells interact and exchange nerve signals (i.e., synapses) and which is involved in numerous physiological processes. Aberrant regulation of BDNF signaling and alterations in synapse activity (i.e., synaptic plasticity) have been associated with the pathophysiology of stress-related disorders and alcoholism. Mechanisms that contribute to the regulation of genetic information without modification of the DNA sequence (i.e., epigenetic mechanisms) may play a role in the complex control of BDNF signaling and synaptic plasticity—for example, by modifying the structure of the DNA–protein complexes (i.e., chromatin) that make up the chromosomes and thereby modulating the expression of certain genes. Studies regarding the epigenetic control of BDNF signaling and synaptic plasticity provide a promising direction to understand the mechanisms mediating the interaction between stress and alcoholism. PMID:23584115

  11. Epigenetics and cerebral organoids:promising directions in autism spectrum disorders

    OpenAIRE

    Forsberg, Sheena Louise; Ilieva, Mirolyuba; Maria Michel, Tanja

    2018-01-01

    Autism spectrum disorders (ASD) affect 1 in 68 children in the US according to the Centers for Disease Control and Prevention (CDC). It is characterized by impairments in social interactions and communication, restrictive and repetitive patterns of behaviors, and interests. Owing to disease complexity, only a limited number of treatment options are available mainly for children that alleviate but do not cure the debilitating symptoms. Studies confirm a genetic link, but environmental factors,...

  12. Epigenetics Research on the International Space Station

    Science.gov (United States)

    Love, John; Cooley, Vic

    2016-01-01

    The International Space Station (ISS) is a state-of-the orbiting laboratory focused on advancing science and technology research. Experiments being conducted on the ISS include investigations in the emerging field of Epigenetics. Epigenetics refers to stably heritable changes in gene expression or cellular phenotype (the transcriptional potential of a cell) resulting from changes in a chromosome without alterations to the underlying DNA nucleotide sequence (the genetic code), which are caused by external or environmental factors, such as spaceflight microgravity. Molecular mechanisms associated with epigenetic alterations regulating gene expression patterns include covalent chemical modifications of DNA (e.g., methylation) or histone proteins (e.g., acetylation, phorphorylation, or ubiquitination). For example, Epigenetics ("Epigenetics in Spaceflown C. elegans") is a recent JAXA investigation examining whether adaptations to microgravity transmit from one cell generation to another without changing the basic DNA of the organism. Mouse Epigenetics ("Transcriptome Analysis and Germ-Cell Development Analysis of Mice in Space") investigates molecular alterations in organ-specific gene expression patterns and epigenetic modifications, and analyzes murine germ cell development during long term spaceflight, as well as assessing changes in offspring DNA. NASA's first foray into human Omics research, the Twins Study ("Differential effects of homozygous twin astronauts associated with differences in exposure to spaceflight factors"), includes investigations evaluating differential epigenetic effects via comprehensive whole genome analysis, the landscape of DNA and RNA methylation, and biomolecular changes by means of longitudinal integrated multi-omics research. And the inaugural Genes in Space student challenge experiment (Genes in Space-1) is aimed at understanding how epigenetics plays a role in immune system dysregulation by assaying DNA methylation in immune cells

  13. Placental FKBP5 genetic and epigenetic variation is associated with infant neurobehavioral outcomes in the RICHS cohort.

    Directory of Open Access Journals (Sweden)

    Alison G Paquette

    a genotype specific fashion, and genetic variation supersedes this effect. These genetic and epigenetic differences in expression may alter the placenta's ability to modulate cortisol response and exposure, leading to altered neurobehavioral outcomes.

  14. Counseling Customers: Emerging Roles for Genetic Counselors in the Direct-to-Consumer Genetic Testing Market

    NARCIS (Netherlands)

    Harris, A.; Kelly, S.; Wyatt, S.

    2013-01-01

    Individuals now have access to an increasing number of internet resources offering personal genomics services. As the direct-to-consumer genetic testing (DTC GT) industry expands, critics have called for pre- and post-test genetic counseling to be included with the product. Several genetic testing

  15. Functional, genetic and epigenetic aspects of base and nucleotide excision repair in colorectal carcinomas

    Czech Academy of Sciences Publication Activity Database

    Slyšková, Jana; Korenková, Vlasta; Collins, A. R.; Procházka, Pavel; Vodičková, Ludmila; Švec, Jiří; Lipská, L.; Levý, M.; Schneiderová, M.; Liška, V.; Holubec, L.; Kumar, R.; Souček, P.; Naccarati, Alessio; Vodička, Pavel

    2012-01-01

    Roč. 18, č. 21 (2012), s. 5878-5887 ISSN 1078-0432 R&D Projects: GA ČR GAP304/12/1585; GA ČR(CZ) GAP304/10/1286; GA MZd NT12025 Grant - others:UICC(XE) ICR/11/068/2011; EEA-research fund:(NO) B/CZ0046/40031 Institutional research plan: CEZ:AV0Z50390512 Institutional support: RVO:68378041 ; RVO:86652036 Keywords : DNA repair capacity * DNA repair gene expression * methylation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.837, year: 2012

  16. Genetic and epigenetic status of triple exotic consanguinity cotton introgression lines.

    Science.gov (United States)

    He, S P; Sun, J L; Du, X M

    2011-10-03

    Introgression lines are some of the most important germplasm for breeding applications and other research conducted on cotton crops. The DNA methylation level among 10 introgression lines of cotton (Gossypium hirsutum) and three exotic parental species (G. arboreum, G. thurberi and G. barbadense) were assessed by methylation-sensitive amplified polymorphism (MSAP) technology. The methylation level in the introgression lines ranged from 33.3 to 51.5%. However, the lines PD0111 and PD0113 had the lowest methylation level (34.6 and 33.3%, respectively) due to demethylation of most non-coding sequences. Amplified fragment length polymorphism (AFLP) was used to evaluate the genetic polymorphism in the cotton introgression lines. A high degree of polymorphism was observed in all introgression lines (mean 47.2%) based on AFLP and MSAP analyses. This confirmed the effects of genetic improvement on cotton introgression lines. The low methylation varieties, PD0111 and PD0113 (introgression lines), clustered outside of the introgression lines based on MSAP data, which was incongruent with an AFLP-based dendrogram. This phenomenon could be caused by environmental changes or introgression of exotic DNA fragments.

  17. Strategies for integrated analysis of genetic, epigenetic and gene expression variation in cancer: addressing the challenges

    Directory of Open Access Journals (Sweden)

    Louise Bruun Thingholm

    2016-02-01

    Full Text Available The development and progression of cancer, a collection of diseases with complex genetic architectures, is facilitated by the interplay of multiple etiological factors. This complexity challenges the traditional single-platform study design and calls for an integrated approach to data analysis. However, integration of heterogeneous measurements of biological variation is a non-trivial exercise due to the diversity of the human genome and the variety of output data formats and genome coverage obtained from the commonly used molecular platforms. This review article will provide an introduction to integration strategies used for analyzing genetic risk factors for cancer. We critically examine the ability of these strategies to handle the complexity of the human genome and also accommodate information about the biological and functional interactions between the elements that have been measured – making the assessment of disease risk against a composite genomic factor possible. The focus of this review is to provide an overview and introduction to the main strategies and to discuss where there is a need for further development.

  18. Genetic counseling and the ethical issues around direct to consumer genetic testing.

    Science.gov (United States)

    Hawkins, Alice K; Ho, Anita

    2012-06-01

    Over the last several years, direct to consumer(DTC) genetic testing has received increasing attention in the public, healthcare and academic realms. DTC genetic testing companies face considerable criticism and scepticism,particularly from the medical and genetic counseling community. This raises the question of what specific aspects of DTC genetic testing provoke concerns, and conversely,promises, for genetic counselors. This paper addresses this question by exploring DTC genetic testing through an ethic allens. By considering the fundamental ethical approaches influencing genetic counseling (the ethic of care and principle-based ethics) we highlight the specific ethical concerns raised by DTC genetic testing companies. Ultimately,when considering the ethics of DTC testing in a genetic counseling context, we should think of it as a balancing act. We need careful and detailed consideration of the risks and troubling aspects of such testing, as well as the potentially beneficial direct and indirect impacts of the increased availability of DTC genetic testing. As a result it is essential that genetic counselors stay informed and involved in the ongoing debate about DTC genetic testing and DTC companies. Doing so will ensure that the ethical theories and principles fundamental to the profession of genetic counseling are promoted not just in traditional counseling sessions,but also on a broader level. Ultimately this will help ensure that the public enjoys the benefits of an increasingly genetic based healthcare system.

  19. Epigenetics and obesity.

    Science.gov (United States)

    Campión, Javier; Milagro, Fermin; Martínez, J Alfredo

    2010-01-01

    The etiology of obesity is multifactorial, involving complex interactions among the genetic makeup, neuroendocrine status, fetal programming, and different unhealthy environmental factors, such as sedentarism or inadequate dietary habits. Among the different mechanisms causing obesity, epigenetics, defined as the study of heritable changes in gene expression that occur without a change in the DNA sequence, has emerged as a very important determinant. Experimental evidence concerning dietary factors influencing obesity development through epigenetic mechanisms has been described. Thus, identification of those individuals who present with changes in DNA methylation profiles, certain histone modifications, or other epigenetically related processes could help to predict their susceptibility to gain or lose weight. Indeed, research concerning epigenetic mechanisms affecting weight homeostasis may play a role in the prevention of excessive fat deposition, the prediction of the most appropriate weight reduction plan, and the implementation of newer therapeutic approaches. Copyright © 2010 Elsevier Inc. All rights reserved.

  20. Evolution of genetic architecture under directional selection.

    Science.gov (United States)

    Hansen, Thomas F; Alvarez-Castro, José M; Carter, Ashley J R; Hermisson, Joachim; Wagner, Günter P

    2006-08-01

    We investigate the multilinear epistatic model under mutation-limited directional selection. We confirm previous results that only directional epistasis, in which genes on average reinforce or diminish each other's effects, contribute to the initial evolution of mutational effects. Thus, either canalization or decanalization can occur under directional selection, depending on whether positive or negative epistasis is prevalent. We then focus on the evolution of the epistatic coefficients themselves. In the absence of higher-order epistasis, positive pairwise epistasis will tend to weaken relative to additive effects, while negative pairwise epistasis will tend to become strengthened. Positive third-order epistasis will counteract these effects, while negative third-order epistasis will reinforce them. More generally, gene interactions of all orders have an inherent tendency for negative changes under directional selection, which can only be modified by higher-order directional epistasis. We identify three types of nonadditive quasi-equilibrium architectures that, although not strictly stable, can be maintained for an extended time: (1) nondirectional epistatic architectures; (2) canalized architectures with strong epistasis; and (3) near-additive architectures in which additive effects keep increasing relative to epistasis.

  1. Integrated genetic and epigenetic analysis identifies haplotype-specific methylation in the FTO type 2 diabetes and obesity susceptibility locus.

    Directory of Open Access Journals (Sweden)

    Christopher G Bell

    2010-11-01

    Full Text Available Recent multi-dimensional approaches to the study of complex disease have revealed powerful insights into how genetic and epigenetic factors may underlie their aetiopathogenesis. We examined genotype-epigenotype interactions in the context of Type 2 Diabetes (T2D, focussing on known regions of genomic susceptibility. We assayed DNA methylation in 60 females, stratified according to disease susceptibility haplotype using previously identified association loci. CpG methylation was assessed using methylated DNA immunoprecipitation on a targeted array (MeDIP-chip and absolute methylation values were estimated using a Bayesian algorithm (BATMAN. Absolute methylation levels were quantified across LD blocks, and we identified increased DNA methylation on the FTO obesity susceptibility haplotype, tagged by the rs8050136 risk allele A (p = 9.40×10(-4, permutation p = 1.0×10(-3. Further analysis across the 46 kb LD block using sliding windows localised the most significant difference to be within a 7.7 kb region (p = 1.13×10(-7. Sequence level analysis, followed by pyrosequencing validation, revealed that the methylation difference was driven by the co-ordinated phase of CpG-creating SNPs across the risk haplotype. This 7.7 kb region of haplotype-specific methylation (HSM, encapsulates a Highly Conserved Non-Coding Element (HCNE that has previously been validated as a long-range enhancer, supported by the histone H3K4me1 enhancer signature. This study demonstrates that integration of Genome-Wide Association (GWA SNP and epigenomic DNA methylation data can identify potential novel genotype-epigenotype interactions within disease-associated loci, thus providing a novel route to aid unravelling common complex diseases.

  2. Repeat-mediated genetic and epigenetic changes at the FMR1 locus in the Fragile X-related disorders

    Science.gov (United States)

    Usdin, Karen; Hayward, Bruce E.; Kumari, Daman; Lokanga, Rachel A.; Sciascia, Nicholas; Zhao, Xiao-Nan

    2014-01-01

    The Fragile X-related disorders are a group of genetic conditions that include the neurodegenerative disorder, Fragile X-associated tremor/ataxia syndrome (FXTAS), the fertility disorder, Fragile X-associated primary ovarian insufficiency (FXPOI) and the intellectual disability, Fragile X syndrome (FXS). The pathology in all these diseases is related to the number of CGG/CCG-repeats in the 5′ UTR of the Fragile X mental retardation 1 (FMR1) gene. The repeats are prone to continuous expansion and the increase in repeat number has paradoxical effects on gene expression increasing transcription on mid-sized alleles and decreasing it on longer ones. In some cases the repeats can simultaneously both increase FMR1 mRNA production and decrease the levels of the FMR1 gene product, Fragile X mental retardation 1 protein (FMRP). Since FXTAS and FXPOI result from the deleterious consequences of the expression of elevated levels of FMR1 mRNA and FXS is caused by an FMRP deficiency, the clinical picture is turning out to be more complex than once appreciated. Added complications result from the fact that increasing repeat numbers make the alleles somatically unstable. Thus many individuals have a complex mixture of different sized alleles in different cells. Furthermore, it has become apparent that the eponymous fragile site, once thought to be no more than a useful diagnostic criterion, may have clinical consequences for females who inherit chromosomes that express this site. This review will cover what is currently known about the mechanisms responsible for repeat instability, for the repeat-mediated epigenetic changes that affect expression of the FMR1 gene, and for chromosome fragility. It will also touch on what current and future options are for ameliorating some of these effects. PMID:25101111

  3. A transposon-directed epigenetic change in ZmCCT underlies quantitative resistance to Gibberella stalk rot in maize.

    Science.gov (United States)

    Wang, Chao; Yang, Qin; Wang, Weixiang; Li, Yipu; Guo, Yanling; Zhang, Dongfeng; Ma, Xuena; Song, Wei; Zhao, Jiuran; Xu, Mingliang

    2017-09-01

    A major resistance quantitative trait locus, qRfg1, significantly enhances maize resistance to Gibberella stalk rot, a devastating disease caused by Fusarium graminearum. However, the underlying molecular mechanism remains unknown. We adopted a map-based cloning approach to identify the resistance gene at qRfg1 and examined the dynamic epigenetic changes during qRfg1-mediated maize resistance to the disease. A CCT domain-containing gene, ZmCCT, is the causal gene at the qRfg1 locus and a polymorphic CACTA-like transposable element (TE1) c. 2.4 kb upstream of ZmCCT is the genetic determinant of allelic variation. The non-TE1 ZmCCT allele is in a poised state, with predictive bivalent chromatin enriched for both repressive (H3K27me3/H3K9me3) and active (H3K4me3) histone marks. Upon pathogen challenge, this non-TE1 ZmCCT allele was promptly induced by a rapid yet transient reduction in H3K27me3/H3K9me3 and a progressive decrease in H3K4me3, leading to disease resistance. However, TE1 insertion in ZmCCT caused selective depletion of H3K4me3 and enrichment of methylated GC to suppress the pathogen-induced ZmCCT expression, resulting in disease susceptibility. Moreover, ZmCCT-mediated resistance to Gibberella stalk rot is not affected by photoperiod sensitivity. This chromatin-based regulatory mechanism enables ZmCCT to be more precise and timely in defense against F. graminearum infection. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  4. Integrative Genetic and Epigenetic Analysis Uncovers Regulatory Mechanisms of Autoimmune Disease.

    Science.gov (United States)

    Shooshtari, Parisa; Huang, Hailiang; Cotsapas, Chris

    2017-07-06

    Genome-wide association studies in autoimmune and inflammatory diseases (AID) have uncovered hundreds of loci mediating risk. These associations are preferentially located in non-coding DNA regions and in particular in tissue-specific DNase I hypersensitivity sites (DHSs). While these analyses clearly demonstrate the overall enrichment of disease risk alleles on gene regulatory regions, they are not designed to identify individual regulatory regions mediating risk or the genes under their control, and thus uncover the specific molecular events driving disease risk. To do so we have departed from standard practice by identifying regulatory regions which replicate across samples and connect them to the genes they control through robust re-analysis of public data. We find significant evidence of regulatory potential in 78/301 (26%) risk loci across nine autoimmune and inflammatory diseases, and we find that individual genes are targeted by these effects in 53/78 (68%) of these. Thus, we are able to generate testable mechanistic hypotheses of the molecular changes that drive disease risk. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  5. Epigenetic developmental programs and adipogenesis: implications for psychotropic induced obesity.

    Science.gov (United States)

    Chase, Kayla; Sharma, Rajiv P

    2013-11-01

    Psychotropic agents are notorious for their ability to increase fat mass in psychiatric patients. The two determinants of fat mass are the production of newly differentiated adipocytes (adipogenesis), and the volume of lipid accumulation. Epigenetic programs have a prominent role in cell fate commitments and differentiation required for adipogenesis. In parallel, epigenetic effects on energy metabolism are well supported by several genetic models. Consequently, a variety of psychotropics, often prescribed in combinations and for long periods, may utilize a common epigenetic effector path causing an increase in adipogenesis or reduction in energy metabolism. In particular, the recent discovery that G protein coupled signaling cascades can directly modify epigenetic regulatory enzymes implicates surface receptor activity by psychotropic medications. The potential therapeutic implications are also suggested by the effects of the clinically approved antidepressant tranylcypromine, also a histone demethylase inhibitor, which has impressive therapeutic effects on metabolism in the obese phenotype.

  6. Epigenetics of autism spectrum disorders.

    Science.gov (United States)

    Schanen, N Carolyn

    2006-10-15

    The autism spectrum disorders (ASD) comprise a complex group of behaviorally related disorders that are primarily genetic in origin. Involvement of epigenetic regulatory mechanisms in the pathogenesis of ASD has been suggested by the occurrence of ASD in patients with disorders arising from epigenetic mutations (fragile X syndrome) or that involve key epigenetic regulatory factors (Rett syndrome). Moreover, the most common recurrent cytogenetic abnormalities in ASD involve maternally derived duplications of the imprinted domain on chromosome 15q11-13. Thus, parent of origin effects on sharing and linkage to imprinted regions on chromosomes 15q and 7q suggest that these regions warrant specific examination from an epigenetic perspective, particularly because epigenetic modifications do not change the primary genomic sequence, allowing risk epialleles to evade detection using standard screening strategies. This review examines the potential role of epigenetic factors in the etiology of ASD.

  7. Epigenetic effects of human breast milk.

    Science.gov (United States)

    Verduci, Elvira; Banderali, Giuseppe; Barberi, Salvatore; Radaelli, Giovanni; Lops, Alessandra; Betti, Federica; Riva, Enrica; Giovannini, Marcello

    2014-04-24

    A current aim of nutrigenetics is to personalize nutritional practices according to genetic variations that influence the way of digestion and metabolism of nutrients introduced with the diet. Nutritional epigenetics concerns knowledge about the effects of nutrients on gene expression. Nutrition in early life or in critical periods of development, may have a role in modulating gene expression, and, therefore, have later effects on health. Human breast milk is well-known for its ability in preventing several acute and chronic diseases. Indeed, breastfed children may have lower risk of neonatal necrotizing enterocolitis, infectious diseases, and also of non-communicable diseases, such as obesity and related-disorders. Beneficial effects of human breast milk on health may be associated in part with its peculiar components, possible also via epigenetic processes. This paper discusses about presumed epigenetic effects of human breast milk and components. While evidence suggests that a direct relationship may exist of some components of human breast milk with epigenetic changes, the mechanisms involved are still unclear. Studies have to be conducted to clarify the actual role of human breast milk on genetic expression, in particular when linked to the risk of non-communicable diseases, to potentially benefit the infant's health and his later life.

  8. Epigenetic Effects of Human Breast Milk

    Directory of Open Access Journals (Sweden)

    Elvira Verduci

    2014-04-01

    Full Text Available A current aim of nutrigenetics is to personalize nutritional practices according to genetic variations that influence the way of digestion and metabolism of nutrients introduced with the diet. Nutritional epigenetics concerns knowledge about the effects of nutrients on gene expression. Nutrition in early life or in critical periods of development, may have a role in modulating gene expression, and, therefore, have later effects on health. Human breast milk is well-known for its ability in preventing several acute and chronic diseases. Indeed, breastfed children may have lower risk of neonatal necrotizing enterocolitis, infectious diseases, and also of non-communicable diseases, such as obesity and related-disorders. Beneficial effects of human breast milk on health may be associated in part with its peculiar components, possible also via epigenetic processes. This paper discusses about presumed epigenetic effects of human breast milk and components. While evidence suggests that a direct relationship may exist of some components of human breast milk with epigenetic changes, the mechanisms involved are still unclear. Studies have to be conducted to clarify the actual role of human breast milk on genetic expression, in particular when linked to the risk of non-communicable diseases, to potentially benefit the infant’s health and his later life.

  9. Nutrition, epigenetic mechanisms, and human disease

    National Research Council Canada - National Science Library

    Maulik, Nilanjana; Maulik, Gautam

    2011-01-01

    .... The text discusses the basics of nutrigenomics and epigenetic regulation, types of nutrition influencing genetic imprinting, and the role of nutrition in modulating an individual's predisposition to disease...

  10. Epigenetics of reproductive infertility.

    Science.gov (United States)

    Das, Laxmidhar; Parbin, Sabnam; Pradhan, Nibedita; Kausar, Chahat; Patra, Samir K

    2017-06-01

    Infertility is a complex pathophysiological condition. It may caused by specific or multiple physical and physiological factors, including abnormalities in homeostasis, hormonal imbalances and genetic alterations. In recent times various studies implicated that, aberrant epigenetic mechanisms are associated with reproductive infertility. There might be transgenerational effects associated with epigenetic modifications of gametes and studies suggest the importance of alterations in epigenetic modification at early and late stages of gametogenesis. To determine the causes of infertility it is necessary to understand the altered epigenetic modifications of associated gene and mechanisms involved therein. This review is devoted to elucidate the recent mechanistic advances in regulation of genes by epigenetic modification and emphasizes their possible role related to reproductive infertility. It includes environmental, nutritional, hormonal and physiological factors and influence of internal structural architecture of chromatin nucleosomes affecting DNA and histone modifications in both male and female gametes, early embryogenesis and offspring. Finally, we would like to emphasize that research on human infertility by gene knock out of epigenetic modifiers genes must be relied upon animal models.

  11. p16(INK4a suppression by glucose restriction contributes to human cellular lifespan extension through SIRT1-mediated epigenetic and genetic mechanisms.

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    Yuanyuan Li

    2011-02-01

    Full Text Available Although caloric restriction (CR has been shown to increase lifespan in various animal models, the mechanisms underlying this phenomenon have not yet been revealed. We developed an in vitro system to mimic CR by reducing glucose concentration in cell growth medium which excludes metabolic factors and allows assessment of the effects of CR at the cellular and molecular level. We monitored cellular proliferation of normal WI-38, IMR-90 and MRC-5 human lung fibroblasts and found that glucose restriction (GR can inhibit cellular senescence and significantly extend cellular lifespan compared with cells receiving normal glucose (NG in the culture medium. Moreover, GR decreased expression of p16(INK4a (p16, a well-known senescence-related gene, in all of the tested cell lines. Over-expressed p16 resulted in early replicative senescence in glucose-restricted cells suggesting a crucial role of p16 regulation in GR-induced cellular lifespan extension. The decreased expression of p16 was partly due to GR-induced chromatin remodeling through effects on histone acetylation and methylation of the p16 promoter. GR resulted in an increased expression of SIRT1, a NAD-dependent histone deacetylase, which has positive correlation with CR-induced longevity. The elevated SIRT1 was accompanied by enhanced activation of the Akt/p70S6K1 signaling pathway in response to GR. Furthermore, knockdown of SIRT1 abolished GR-induced p16 repression as well as Akt/p70S6K1 activation implying that SIRT1 may affect p16 repression through direct deacetylation effects and indirect regulation of Akt/p70S6K1 signaling. Collectively, these results provide new insights into interactions between epigenetic and genetic mechanisms on CR-induced longevity that may contribute to anti-aging approaches and also provide a general molecular model for studying CR in vitro in mammalian systems.

  12. Epigenetics: What it is about?

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    Saade E.

    2014-01-01

    Full Text Available Epigenetics has captured the attention of scientists in the past decades, yet its scope has been continuously changing. In this paper, we give an overview on how and why its definition has evolved and suggest several clarification on the concepts used in this field. Waddington coined the term in 1942 to describe genes interaction with each other and with their environment and insisted on dissociating these events from development. Then, Holliday and others argued that epigenetic phenomena are characterized by their heritability. However, differentiated cells can maintain their phenotypes for decades without undergoing division, which points out the limitation of the «heritability» criterion for a particular phenomenon to qualify as epigenetic. «Epigenetic stability» encompasses traits preservation in both dividing and non dividing cells. Likewise, the use of the term «epigenetic regulation» has been misleading as it overlaps with «regulation of gene expression», whereas «epigenetic information» clearly distinguishes epigenetic from genetic phenomena. Consequently, how could epigenetic information be transmitted and perpetuated? The term «epigenetic templating» has been proposed to refer to a general mechanism of perpetuation of epigenetic information that is based on the preferential activity of enzymes that deposit a particular epigenetic mark on macromolecular complexes already containing the same mark. Another issue that we address is the role of epigenetic information. Not only it is important in allowing alternative interpretations of genetic information, but it appears to be important in protecting the genome, as can be illustrated by bacterial endonucleases that targets non methylated DNA – i. e. foreign DNA – and not the endogenous methylated DNA.

  13. Scrutinizing the epigenetics revolution

    Science.gov (United States)

    Meloni, Maurizio; Testa, Giuseppe

    2014-01-01

    Epigenetics is one of the most rapidly expanding fields in the life sciences. Its rise is frequently framed as a revolutionary turn that heralds a new epoch both for gene-based epistemology and for the wider discourse on life that pervades knowledge-intensive societies of the molecular age. The fundamentals of this revolution remain however to be scrutinized, and indeed the very contours of what counts as ‘epigenetic' are often blurred. This is reflected also in the mounting discourse on the societal implications of epigenetics, in which vast expectations coexist with significant uncertainty about what aspects of this science are most relevant for politics or policy alike. This is therefore a suitable time to reflect on the directions that social theory could most productively take in the scrutiny of this revolution. Here we take this opportunity in both its scholarly and normative dimension, that is, proposing a roadmap for social theorizing on epigenetics that does not shy away from, and indeed hopefully guides, the framing of its most socially relevant outputs. To this end, we start with an epistemological reappraisal of epigenetic discourse that valorizes the blurring of meanings as a critical asset for the field and privileged analytical entry point. We then propose three paths of investigation. The first looks at the structuring elements of controversies and visions around epigenetics. The second probes the mutual constitution between the epigenetic reordering of living phenomena and the normative settlements that orient individual and collective responsibilities. The third highlights the material import of epigenetics and the molecularization of culture that it mediates. We suggest that these complementary strands provide both an epistemically and socially self-reflective framework to advance the study of epigenetics as a molecular juncture between nature and nurture and thus as the new critical frontier in the social studies of the life sciences. PMID

  14. Network Biomarkers of Bladder Cancer Based on a Genome-Wide Genetic and Epigenetic Network Derived from Next-Generation Sequencing Data.

    Science.gov (United States)

    Li, Cheng-Wei; Chen, Bor-Sen

    2016-01-01

    Epigenetic and microRNA (miRNA) regulation are associated with carcinogenesis and the development of cancer. By using the available omics data, including those from next-generation sequencing (NGS), genome-wide methylation profiling, candidate integrated genetic and epigenetic network (IGEN) analysis, and drug response genome-wide microarray analysis, we constructed an IGEN system based on three coupling regression models that characterize protein-protein interaction networks (PPINs), gene regulatory networks (GRNs), miRNA regulatory networks (MRNs), and epigenetic regulatory networks (ERNs). By applying system identification method and principal genome-wide network projection (PGNP) to IGEN analysis, we identified the core network biomarkers to investigate bladder carcinogenic mechanisms and design multiple drug combinations for treating bladder cancer with minimal side-effects. The progression of DNA repair and cell proliferation in stage 1 bladder cancer ultimately results not only in the derepression of miR-200a and miR-200b but also in the regulation of the TNF pathway to metastasis-related genes or proteins, cell proliferation, and DNA repair in stage 4 bladder cancer. We designed a multiple drug combination comprising gefitinib, estradiol, yohimbine, and fulvestrant for treating stage 1 bladder cancer with minimal side-effects, and another multiple drug combination comprising gefitinib, estradiol, chlorpromazine, and LY294002 for treating stage 4 bladder cancer with minimal side-effects.

  15. Epigenetics: a new frontier in dentistry.

    Science.gov (United States)

    Williams, S D; Hughes, T E; Adler, C J; Brook, A H; Townsend, G C

    2014-06-01

    In 2007, only four years after the completion of the Human Genome Project, the journal Science announced that epigenetics was the 'breakthrough of the year'. Time magazine placed it second in the top 10 discoveries of 2009. While our genetic code (i.e. our DNA) contains all of the information to produce the elements we require to function, our epigenetic code determines when and where genes in the genetic code are expressed. Without the epigenetic code, the genetic code is like an orchestra without a conductor. Although there is now a substantial amount of published research on epigenetics in medicine and biology, epigenetics in dental research is in its infancy. However, epigenetics promises to become increasingly relevant to dentistry because of the role it plays in gene expression during development and subsequently potentially influencing oral disease susceptibility. This paper provides a review of the field of epigenetics aimed specifically at oral health professionals. It defines epigenetics, addresses the underlying concepts and provides details about specific epigenetic molecular mechanisms. Further, we discuss some of the key areas where epigenetics is implicated, and review the literature on epigenetics research in dentistry, including its relevance to clinical disciplines. This review considers some implications of epigenetics for the future of dental practice, including a 'personalized medicine' approach to the management of common oral diseases. © 2014 Australian Dental Association.

  16. A map of directional genetic interactions in a metazoan cell.

    Science.gov (United States)

    Fischer, Bernd; Sandmann, Thomas; Horn, Thomas; Billmann, Maximilian; Chaudhary, Varun; Huber, Wolfgang; Boutros, Michael

    2015-03-06

    Gene-gene interactions shape complex phenotypes and modify the effects of mutations during development and disease. The effects of statistical gene-gene interactions on phenotypes have been used to assign genes to functional modules. However, directional, epistatic interactions, which reflect regulatory relationships between genes, have been challenging to map at large-scale. Here, we used combinatorial RNA interference and automated single-cell phenotyping to generate a large genetic interaction map for 21 phenotypic features of Drosophila cells. We devised a method that combines genetic interactions on multiple phenotypes to reveal directional relationships. This network reconstructed the sequence of protein activities in mitosis. Moreover, it revealed that the Ras pathway interacts with the SWI/SNF chromatin-remodelling complex, an interaction that we show is conserved in human cancer cells. Our study presents a powerful approach for reconstructing directional regulatory networks and provides a resource for the interpretation of functional consequences of genetic alterations.

  17. Rubinstein-Taybi Syndrome and Epigenetic Alterations.

    Science.gov (United States)

    Korzus, Edward

    2017-01-01

    Rubinstein-Taybi syndrome (RSTS) is a rare genetic disorder in humans characterized by growth and psychomotor delay, abnormal gross anatomy, and mild to severe mental retardation (Rubinstein and Taybi, Am J Dis Child 105:588-608, 1963, Hennekam et al., Am J Med Genet Suppl 6:56-64, 1990). RSTS is caused by de novo mutations in epigenetics-associated genes, including the cAMP response element-binding protein (CREBBP), the gene-encoding protein referred to as CBP, and the EP300 gene, which encodes the p300 protein, a CBP homologue. Recent studies of the epigenetic mechanisms underlying cognitive functions in mice provide direct evidence for the involvement of nuclear factors (e.g., CBP) in the control of higher cognitive functions. In fact, a role for CBP in higher cognitive function is suggested by the finding that RSTS is caused by heterozygous mutations at the CBP locus (Petrij et al., Nature 376:348-351, 1995). CBP was demonstrated to possess an intrinsic histone acetyltransferase activity (Ogryzko et al., Cell 87:953-959, 1996) that is required for CREB-mediated gene expression (Korzus et al., Science 279:703-707, 1998). The intrinsic protein acetyltransferase activity in CBP might directly destabilize promoter-bound nucleosomes, facilitating the activation of transcription. Due to the complexity of developmental abnormalities and the possible genetic compensation associated with this congenital disorder, however, it is difficult to establish a direct role for CBP in cognitive function in the adult brain. Although aspects of the clinical presentation in RSTS cases have been extensively studied, a spectrum of symptoms found in RSTS patients can be accessed only after birth, and, thus, prenatal genetic tests for this extremely rare genetic disorder are seldom considered. Even though there has been intensive research on the genetic and epigenetic function of the CREBBP gene in rodents, the etiology of this devastating congenital human disorder is largely unknown.

  18. Nutritional epigenetics

    Science.gov (United States)

    This chapter is intended to provide a timely overview of the current state of research at the intersection of nutrition and epigenetics. I begin by describing epigenetics and molecular mechanisms of eigenetic regulation, then highlight four classes of nutritional exposures currently being investiga...

  19. Genetic-and-epigenetic Interspecies Networks for Cross-talk Mechanisms in Human Macrophages and Dendritic Cells During MTB Infection

    Directory of Open Access Journals (Sweden)

    Cheng-Wei Li

    2016-10-01

    Full Text Available Tuberculosis is caused by Mycobacterium tuberculosis (Mtb infection. Mtb is one of the oldest human pathogens, and evolves mechanisms implied in human evolution. The lungs are the first organ exposed to aerosol-transmitted Mtb during gaseous exchange. Therefore, the guards of the immune system in the lungs, such as macrophages (Mϕs and dendritic cells (DCs, are the most important defense against Mtb infection. There have been several studies discussing the functions of Mϕs and DCs during Mtb infection, but the genome-wide pathways and networks are still incomplete. Furthermore, the immune response induced by Mϕs and DCs varies. Therefore, we analyzed the cross-talk genome-wide genetic-and-epigenetic interspecies networks (GWGEINs between Mϕs vs. Mtb and DCs vs. Mtb to determine the varying mechanisms of both the host and pathogen as it relates to Mϕs and DCs during early Mtb infection.First, we performed database mining to construct candidate cross-talk GWGEIN between human cells and Mtb. Then we constructed dynamic models to characterize the molecular mechanisms, including intraspecies gene/microRNA (miRNA regulation networks (GRNs, intraspecies protein-protein interaction networks (PPINs, and the interspecies PPIN of the cross-talk GWGEIN. We applied a system identification method and a system order detection scheme to dynamic models to identify the real cross-talk GWGEINs using the microarray data of Mϕs, DCs and Mtb.After identifying the real cross-talk GWGEINs, the principal network projection (PNP method was employed to construct host-pathogen core networks (HPCNs between Mϕs vs. Mtb and DCs vs. Mtb during infection process. Thus, we investigated the underlying cross-talk mechanisms between the host and the pathogen to determine how the pathogen counteracts host defense mechanisms in Mϕs and DCs during Mtb H37Rv early infection. Based on our findings, we propose Rv1675c as a potential drug target because of its important defensive

  20. How stable 'should' epigenetic modifications be? Insights from adaptive plasticity and bet hedging.

    Science.gov (United States)

    Herman, Jacob J; Spencer, Hamish G; Donohue, Kathleen; Sultan, Sonia E

    2014-03-01

    Although there is keen interest in the potential adaptive value of epigenetic variation, it is unclear what conditions favor the stability of these variants either within or across generations. Because epigenetic modifications can be environmentally sensitive, existing theory on adaptive phenotypic plasticity provides relevant insights. Our consideration of this theory suggests that stable maintenance of environmentally induced epigenetic states over an organism's lifetime is most likely to be favored when the organism accurately responds to a single environmental change that subsequently remains constant, or when the environmental change cues an irreversible developmental transition. Stable transmission of adaptive epigenetic states from parents to offspring may be selectively favored when environments vary across generations and the parental environment predicts the offspring environment. The adaptive value of stability beyond a single generation of parent-offspring transmission likely depends on the costs of epigenetic resetting. Epigenetic stability both within and across generations will also depend on the degree and predictability of environmental variation, dispersal patterns, and the (epi)genetic architecture underlying phenotypic responses to environment. We also discuss conditions that favor stability of random epigenetic variants within the context of bet hedging. We conclude by proposing research directions to clarify the adaptive significance of epigenetic stability. © 2013 The Author(s). Evolution © 2013 The Society for the Study of Evolution.

  1. Epigenetic Determinism in Science and Society.

    Science.gov (United States)

    Waggoner, Miranda R; Uller, Tobias

    2015-04-03

    The epigenetic "revolution" in science cuts across many disciplines, and it is now one of the fastest growing research areas in biology. Increasingly, claims are made that epigenetics research represents a move away from the genetic determinism that has been prominent both in biological research and in understandings of the impact of biology on society. We discuss to what extent an epigenetic framework actually supports these claims. We show that, in contrast to the received view, epigenetics research is often couched in language as deterministic as genetics research in both science and the popular press. We engage the rapidly emerging conversation about the impact of epigenetics on public discourse and scientific practice, and we contend that the notion of epigenetic determinism - or the belief that epigenetic mechanisms determine the expression of human traits and behaviors - matters for understandings of the influence of biology and society on population health.

  2. Epigenetics of Obesity.

    Science.gov (United States)

    Lopomo, A; Burgio, E; Migliore, L

    2016-01-01

    Obesity is a metabolic disease, which is becoming an epidemic health problem: it has been recently defined in terms of Global Pandemic. Over the years, the approaches through family, twins and adoption studies led to the identification of some causal genes in monogenic forms of obesity but the origins of the pandemic of obesity cannot be considered essentially due to genetic factors, because human genome is not likely to change in just a few years. Epigenetic studies have offered in recent years valuable tools for the understanding of the worldwide spread of the pandemic of obesity. The involvement of epigenetic modifications-DNA methylation, histone tails, and miRNAs modifications-in the development of obesity is more and more evident. In the epigenetic literature, there are evidences that the entire embryo-fetal and perinatal period of development plays a key role in the programming of all human organs and tissues. Therefore, the molecular mechanisms involved in the epigenetic programming require a new and general pathogenic paradigm, the Developmental Origins of Health and Disease theory, to explain the current epidemiological transition, that is, the worldwide increase of chronic, degenerative, and inflammatory diseases such as obesity, diabetes, cardiovascular diseases, neurodegenerative diseases, and cancer. Obesity and its related complications are more and more associated with environmental pollutants (obesogens), gut microbiota modifications and unbalanced food intake, which can induce, through epigenetic mechanisms, weight gain, and altered metabolic consequences. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Transgenerational inheritance or resetting of stress-induced epigenetic modifications: two sides of the same coin.

    Directory of Open Access Journals (Sweden)

    Penny J Tricker

    2015-09-01

    Full Text Available The transgenerational inheritance of stress-induced epigenetic modifications is still controversial. Despite several examples of defence ‘priming’ and induced genetic rearrangements, the involvement and persistence of transgenerational epigenetic modifications is not known to be general. Here I argue that non-transmission of epigenetic marks through meiosis may be regarded as an epigenetic modification in itself, and that we should understand the implications for plant evolution in the context of both selection for and selection against transgenerational epigenetic memory. Recent data suggest that both epigenetic inheritance and resetting are mechanistically directed and targeted. Stress-induced epigenetic modifications may buffer against DNA sequence-based evolution to maintain plasticity, or may form part of plasticity’s adaptive potential. To date we have tended to concentrate on the question of whether and for how long epigenetic memory persists. I argue that we should now re-direct our question to investigate the differences between where it persists and where it does not, to understand the higher order evolutionary methods in play and their contribution.

  4. Transgenerational inheritance or resetting of stress-induced epigenetic modifications: two sides of the same coin.

    Science.gov (United States)

    Tricker, Penny J

    2015-01-01

    The transgenerational inheritance of stress-induced epigenetic modifications is still controversial. Despite several examples of defense "priming" and induced genetic rearrangements, the involvement and persistence of transgenerational epigenetic modifications is not known to be general. Here I argue that non-transmission of epigenetic marks through meiosis may be regarded as an epigenetic modification in itself, and that we should understand the implications for plant evolution in the context of both selection for and selection against transgenerational epigenetic memory. Recent data suggest that both epigenetic inheritance and resetting are mechanistically directed and targeted. Stress-induced epigenetic modifications may buffer against DNA sequence-based evolution to maintain plasticity, or may form part of plasticity's adaptive potential. To date we have tended to concentrate on the question of whether and for how long epigenetic memory persists. I argue that we should now re-direct our question to investigate the differences between where it persists and where it does not, to understand the higher order evolutionary methods in play and their contribution.

  5. Epigenetic control of mobile DNA as an interface between experience and genome change

    Directory of Open Access Journals (Sweden)

    James A. Shapiro

    2014-04-01

    Full Text Available Mobile DNA in the genome is subject to RNA-targeted epigenetic control. This control regulates the activity of transposons, retrotransposons and genomic proviruses. Many different life history experiences alter the activities of mobile DNA and the expression of genetic loci regulated by nearby insertions. The same experiences induce alterations in epigenetic formatting and lead to trans-generational modifications of genome expression and stability. These observations lead to the hypothesis that epigenetic formatting directed by non-coding RNA provides a molecular interface between life history events and genome alteration.

  6. Human adipose-derived mesenchymal stromal cell pigment epithelium-derived factor cytotherapy modifies genetic and epigenetic profiles of prostate cancer cells.

    Science.gov (United States)

    Zolochevska, Olga; Shearer, Joseph; Ellis, Jayne; Fokina, Valentina; Shah, Forum; Gimble, Jeffrey M; Figueiredo, Marxa L

    2014-03-01

    Adipose-derived mesenchymal stromal cells (ASCs) are promising tools for delivery of cytotherapy against cancer. However, ASCs can exert profound effects on biological behavior of tumor cells. Our study aimed to examine the influence of ASCs on gene expression and epigenetic methylation profiles of prostate cancer cells as well as the impact of expressing a therapeutic gene on modifying the interaction between ASCs and prostate cancer cells. ASCs were modified by lentiviral transduction to express either green fluorescent protein as a control or pigment epithelium-derived factor (PEDF) as a therapeutic molecule. PC3 prostate cancer cells were cultured in the presence of ASC culture-conditioned media (CCM), and effects on PC3 or DU145. Ras cells were examined by means of real-time quantitative polymerase chain reaction, EpiTect methyl prostate cancer-focused real-time quantitative polymerase chain reaction arrays, and luciferase reporter assays. ASCs transduced with lentiviral vectors were able to mediate expression of several tumor-inhibitory genes, some of which correlated with epigenetic methylation changes on cocultured PC3 prostate cancer cells. When PC3 cells were cultured with ASC-PEDF CCM, we observed a shift in the balance of gene expression toward tumor inhibition, which suggests that PEDF reduces the potential tumor-promoting activity of unmodified ASCs. These results suggest that ASC-PEDF CCM can promote reprogramming of tumor cells in a paracrine manner. An improved understanding of genetic and epigenetic events in prostate cancer growth in response to PEDF paracrine therapy would enable a more effective use of ASC-PEDF, with the goal of achieving safer yet more potent anti-tumor effects. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  7. Is Glioblastoma an Epigenetic Malignancy?

    International Nuclear Information System (INIS)

    Maleszewska, Marta; Kaminska, Bozena

    2013-01-01

    Epigenetic modifications control gene expression by regulating the access of nuclear proteins to their target DNA and have been implicated in both normal cell differentiation and oncogenic transformation. Epigenetic abnormalities can occur both as a cause and as a consequence of cancer. Oncogenic transformation can deeply alter the epigenetic information enclosed in the pattern of DNA methylation or histone modifications. In addition, in some cancers epigenetic dysfunctions can drive oncogenic transformation. Growing evidence emphasizes the interplay between metabolic disturbances, epigenomic changes and cancer, i.e., mutations in the metabolic enzymes SDH, FH, and IDH may contribute to cancer development. Epigenetic-based mechanisms are reversible and the possibility of “resetting” the abnormal cancer epigenome by applying pharmacological or genetic strategies is an attractive, novel approach. Gliomas are incurable with all current therapeutic approaches and new strategies are urgently needed. Increasing evidence suggests the role of epigenetic events in development and/or progression of gliomas. In this review, we summarize current data on the occurrence and significance of mutations in the epigenetic and metabolic enzymes in pathobiology of gliomas. We discuss emerging therapies targeting specific epigenetic modifications or chromatin modifying enzymes either alone or in combination with other treatment regimens

  8. An in silico approach reveals associations between genetic and epigenetic factors within regulatory elements in B cells from primary Sjögren’s syndrome patients

    Directory of Open Access Journals (Sweden)

    Orsia D. Konsta

    2015-08-01

    Full Text Available Recent advances in genetics have highlighted several regions and candidate genes associated with primary Sjögren's syndrome (SS, a systemic autoimmune epithelitis that combines exocrine gland dysfunctions, and focal lymphocytic infiltrations. In addition to genetic factors, it is now clear that epigenetic deregulations are present during SS and restricted to specific cell type subsets such as lymphocytes and salivary gland epithelial cells. In this study, 72 single nucleotide polymorphisms (SNPs associated with 43 SS gene risk factors were selected from publicly available and peer reviewed literature for further in silico analysis. SS risk variant location was tested revealing a broad distribution in coding sequences (5.6%, intronic sequences (55.6%, upstream/downstream genic regions (30.5%, and intergenic regions (8.3%. Moreover, a significant enrichment of regulatory motifs (promoter, enhancer, insulator, DNAse peak and eQTL characterizes SS risk variants (94.4%. Next, screening SNPs in high linkage disequilibrium (r2 ≥ 0.8 in Caucasians revealed 645 new variants including 5 SNPs with missense mutations, and indicated an enrichment of transcriptionally active motifs according to the cell type (B cells > monocytes > T cells >> A549. Finally, we looked at SS risk variants for histone markers in B cells (GM12878, monocytes (CD14+ and epithelial cells (A548. Active histone markers were associated with SS risk variants at both promoters and enhancers in B cells, and within enhancers in monocytes. In conclusion and based on the obtained in silico results, that need further confirmation, associations were observed between SS genetic risk factors and epigenetic factors and these associations predominate in B cells such as those observed at the FAM167A-BLK locus.

  9. Epigenetic reprogramming of breast cancer cells with oocyte extracts

    Directory of Open Access Journals (Sweden)

    Kumari Rajendra

    2011-01-01

    Full Text Available Abstract Background Breast cancer is a disease characterised by both genetic and epigenetic alterations. Epigenetic silencing of tumour suppressor genes is an early event in breast carcinogenesis and reversion of gene silencing by epigenetic reprogramming can provide clues to the mechanisms responsible for tumour initiation and progression. In this study we apply the reprogramming capacity of oocytes to cancer cells in order to study breast oncogenesis. Results We show that breast cancer cells can be directly reprogrammed by amphibian oocyte extracts. The reprogramming effect, after six hours of treatment, in the absence of DNA replication, includes DNA demethylation and removal of repressive histone marks at the promoters of tumour suppressor genes; also, expression of the silenced genes is re-activated in response to treatment. This activity is specific to oocytes as it is not elicited by extracts from ovulated eggs, and is present at very limited levels in extracts from mouse embryonic stem cells. Epigenetic reprogramming in oocyte extracts results in reduction of cancer cell growth under anchorage independent conditions and a reduction in tumour growth in mouse xenografts. Conclusions This study presents a new method to investigate tumour reversion by epigenetic reprogramming. After testing extracts from different sources, we found that axolotl oocyte extracts possess superior reprogramming ability, which reverses epigenetic silencing of tumour suppressor genes and tumorigenicity of breast cancer cells in a mouse xenograft model. Therefore this system can be extremely valuable for dissecting the mechanisms involved in tumour suppressor gene silencing and identifying molecular activities capable of arresting tumour growth. These applications can ultimately shed light on the contribution of epigenetic alterations in breast cancer and advance the development of epigenetic therapies.

  10. Insights into genetic and epigenetic determinants with impact on vitamin D signaling and cancer association studies: The case of thyroid cancer

    Directory of Open Access Journals (Sweden)

    Gregoire B Morand

    2014-11-01

    Full Text Available Vitamin D is a key regulator of calcium metabolism and has been implicated as a cancer preventive agent. However, clinical studies have revealed conflicting results on its cancer preventive properties, attributed in part to multiple metabolic and regulatory factors susceptible to affect individual responses to exogenous vitamin D. Vitamin D is obtained from dietary sources and sun exposure, which depends on numerous parameters such as skin type, latitude, and lifestyle factors. Focusing on thyroid cancer, we document that genetic and epigenetic determinants can greatly impact individual response to vitamin D and may outweigh the classical clinical correlative studies that focus on sun exposure/dietary intake factors. In particular, genetic determinants innate to host intrinsic metabolic pathways such as highly polymorphic cytochromes P450s responsible for the metabolic activation of vitamin D are expressed in many organs, including the thyroid gland and can impact vitamin D interaction with its nuclear receptor (VDR in thyroid tissue. Moreover, downstream regulatory pathways in vitamin D signalling as well as VDR are also subject to wide genetic variability among human populations as shown by genome-wide studies. These genetic variations in multiple components of vitamin D pathways are critical determinants for the re-valuation of the potential preventive and anticancer properties of vitamin D in thyroid cancer.

  11. Epigenetics and brain evolution.

    Science.gov (United States)

    Keverne, Eric B

    2011-04-01

    Fundamental aspects of mammalian brain evolution occurred in the context of viviparity and placentation brought about by the epigenetic regulation of imprinted genes. Since the fetal placenta hormonally primes the maternal brain, two genomes in one individual are transgenerationally co-adapted to ensure maternal care and nurturing. Advanced aspects of neocortical brain evolution has shown very few genetic changes between monkeys and humans. Although these lineages diverged at approximately the same time as the rat and mouse (20 million years ago), synonymous sequence divergence between the rat and mouse is double that when comparing monkey with human sequences. Paradoxically, encephalization of rat and mouse are remarkably similar, while comparison of the human and monkey shows the human cortex to be three times the size of the monkey. This suggests an element of genetic stability between the brains of monkey and man with a greater emphasis on epigenetics providing adaptable variability.

  12. Autism Spectrum Disorders and Epigenetics

    Science.gov (United States)

    Grafodatskaya, Daria; Chung, Brian; Szatmari, Peter; Weksberg, Rosanna

    2010-01-01

    Objective: Current research suggests that the causes of autism spectrum disorders (ASD) are multifactorial and include both genetic and environmental factors. Several lines of evidence suggest that epigenetics also plays an important role in ASD etiology and that it might, in fact, integrate genetic and environmental influences to dysregulate…

  13. Peromyscus as a Mammalian Epigenetic Model

    Directory of Open Access Journals (Sweden)

    Kimberly R. Shorter

    2012-01-01

    Full Text Available Deer mice (Peromyscus offer an opportunity for studying the effects of natural genetic/epigenetic variation with several advantages over other mammalian models. These advantages include the ability to study natural genetic variation and behaviors not present in other models. Moreover, their life histories in diverse habitats are well studied. Peromyscus resources include genome sequencing in progress, a nascent genetic map, and >90,000 ESTs. Here we review epigenetic studies and relevant areas of research involving Peromyscus models. These include differences in epigenetic control between species and substance effects on behavior. We also present new data on the epigenetic effects of diet on coat-color using a Peromyscus model of agouti overexpression. We suggest that in terms of tying natural genetic variants with environmental effects in producing specific epigenetic effects, Peromyscus models have a great potential.

  14. Epigenetics in Cancer: A Hematological Perspective.

    Directory of Open Access Journals (Sweden)

    Maximilian Stahl

    2016-10-01

    Full Text Available For several decades, we have known that epigenetic regulation is disrupted in cancer. Recently, an increasing body of data suggests epigenetics might be an intersection of current cancer research trends: next generation sequencing, immunology, metabolomics, and cell aging. The new emphasis on epigenetics is also related to the increasing production of drugs capable of interfering with epigenetic mechanisms and able to trigger clinical responses in even advanced phase patients. In this review, we will use myeloid malignancies as proof of concept examples of how epigenetic mechanisms can trigger or promote oncogenesis. We will also show how epigenetic mechanisms are related to genetic aberrations, and how they affect other systems, like immune response. Finally, we will show how we can try to influence the fate of cancer cells with epigenetic therapy.

  15. THE EPIGENETICS OF RENAL CELL TUMORS: FROM BIOLOGY TO BIOMARKERS

    Directory of Open Access Journals (Sweden)

    Rui eHenrique

    2012-05-01

    Full Text Available Renal cell tumors (RCT collectively constitute the third most common type of genitourinary neoplasms, only surpassed by prostate and bladder cancer. They comprise a heterogeneous group of neoplasms with distinctive clinical, morphological and genetic features. Epigenetic alterations are a hallmark of cancer cells and their role in renal tumorigenesis is starting to emerge. Aberrant DNA methylation, altered chromatin remodeling / histone onco-modifications and deregulated microRNA expression not only contribute to the emergence and progression of RCTs, but owing to their ubiquity, they also constitute a promising class of biomarkers tailored for disease detection, diagnosis, assessment of prognosis and prediction of response to therapy. Moreover, due to their dynamic and reversible properties, those alterations represent a target for epigenetic-directed therapies. In this review, the current knowledge about epigenetic mechanisms and their altered status in RCT is summarized and their envisaged use in a clinical setting is also provided.

  16. Epigenetics in autism and other neurodevelopmental diseases.

    Science.gov (United States)

    Miyake, Kunio; Hirasawa, Takae; Koide, Tsuyoshi; Kubota, Takeo

    2012-01-01

    Autism was previously thought to be caused by environmental factors. However, genetic factors are now considered to be more contributory to the pathogenesis of autism, based on the recent findings of mutations in the genes which encode synaptic molecules associated with the communication between neurons. Epigenetic is a mechanism that controls gene expression without changing DNA sequence but by changing chromosomal histone modifications and its abnormality is associated with several neurodevelopmental diseases. Since epigenetic modifications are known to be affected by environmental factors such as nutrition, drugs and mental stress, autistic diseases are not only caused by congenital genetic defects, but may also be caused by environmental factors via epigenetic mechanism. In this chapter, we introduce autistic diseases caused by epigenetic failures and discuss epigenetic changes by environmental factors and discuss new treatments for neurodevelopmental diseases based on the recent epigenetic findings.

  17. Using Epigenetic Therapy to Overcome Chemotherapy Resistance.

    Science.gov (United States)

    Strauss, Julius; Figg, William D

    2016-01-01

    It has been known for decades that as cancer progresses, tumors develop genetic alterations, making them highly prone to developing resistance to therapies. Classically, it has been thought that these acquired genetic changes are fixed. This has led to the paradigm of moving from one cancer therapy to the next while avoiding past therapies. However, emerging data on epigenetic changes during tumor progression and use of epigenetic therapies have shown that epigenetic modifications leading to chemotherapy resistance have the potential to be reversible with epigenetic therapy. In fact, promising clinical data exist that treatment with epigenetic agents can diminish chemotherapy resistance in a number of tumor types including chronic myelogenous leukemia, colorectal, ovarian, lung and breast cancer. The potential for epigenetic-modifying drugs to allow for treatment of resistant disease is exciting and clinical trials have just begun to evaluate this area. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  18. Topographical cues of direct metal laser sintering titanium surfaces facilitate osteogenic differentiation of bone marrow mesenchymal stem cells through epigenetic regulation.

    Science.gov (United States)

    Zheng, Guoying; Guan, Binbin; Hu, Penghui; Qi, Xingying; Wang, Pingting; Kong, Yu; Liu, Zihao; Gao, Ping; Li, Rui; Zhang, Xu; Wu, Xudong; Sui, Lei

    2018-04-27

    To investigate the role of hierarchical micro/nanoscale topography of direct metal laser sintering (DMLS) titanium surfaces in osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), as well as the possible underlying epigenetic mechanism. Three groups of titanium specimens were prepared, including DMLS group, sandblasted, large-grit, acid-etched (SLA) group and smooth titanium (Ti) group. BMSCs were cultured on discs followed by surface characterization. Cell adhesion and proliferation were examined by SEM and CCK-8 assay, while osteogenic-related gene expression was detected by real-time RT-PCR. Immunofluorescence, western blotting and in vivo study were also performed to evaluate the potential for osteogenic induction of materials. In addition, to investigate the underlying epigenetic mechanisms, immunofluorescence and western blotting were performed to evaluate the global level of H3K4me3 during osteogenesis. The H3K4me3 and H3K27me3 levels at the promoter area of the osteogenic gene Runx2 were detected by ChIP assay. The DMLS surface exhibits greater protein adsorption ability and shows better cell adhesion performance than SLA and Ti surfaces. Moreover, both in vitro and in vivo studies demonstrated that the DMLS surface is more favourable for the osteogenic differentiation of BMSCs than SLA and Ti surfaces. Accordingly, osteogenesis-associated gene expression in BMSCs is efficiently induced by a rapid H3K27 demethylation and increase in H3K4me3 levels at gene promoters upon osteogenic differentiation on DMLS titanium surface. Topographical cues of DMLS surfaces have greater potential for the induction of osteogenic differentiation of BMSCs than SLA and Ti surfaces both in vitro and in vivo. A potential epigenetic mechanism is that the appropriate topography allows rapid H3K27 demethylation and an increased H3K4me3 level at the promoter region of osteogenesis-associated genes during the osteogenic differentiation of BMSCs. © 2018 John Wiley

  19. [Advantages and disadvantages of direct-to-consumer genetic tests].

    Science.gov (United States)

    Christiansen, Camilla Worm; Gerdes, Anne-Marie Axø

    2017-03-13

    Direct-to-consumer genetic tests are sold over the internet to consumers all over the world - including Denmark. No regulation of these tests has been introduced neither in Denmark nor in Europe, even though they have been on the market since 2007. Such tests have several advantages, but indeed also a long list of potential disadvantages, which are most often ignored, and among these is insufficient training of general practitioners in performing the necessary counselling but also the risk of increased expenses to unnecessary follow-up consultations.

  20. Epigenetics and Evolution: Transposons and the Stochastic Epigenetic Modification Model

    Directory of Open Access Journals (Sweden)

    Sergio Branciamore

    2015-04-01

    Full Text Available In addition to genetic variation, epigenetic variation and transposons can greatly affect the evolutionary fitnesses landscape and gene expression. Previously we proposed a mathematical treatment of a general epigenetic variation model that we called Stochastic Epigenetic Modification (SEM model. In this study we follow up with a special case, the Transposon Silencing Model (TSM, with, once again, emphasis on quantitative treatment. We have investigated the evolutionary effects of epigenetic changes due to transposon (T insertions; in particular, we have considered a typical gene locus A and postulated that (i the expression level of gene A depends on the epigenetic state (active or inactive of a cis- located transposon element T, (ii stochastic variability in the epigenetic silencing of T occurs only in a short window of opportunity during development, (iii the epigenetic state is then stable during further development, and (iv the epigenetic memory is fully reset at each generation. We develop the model using two complementary approaches: a standard analytical population genetics framework (di usion equations and Monte-Carlo simulations. Both approaches led to similar estimates for the probability of fixation and time of fixation of locus TA with initial frequency P in a randomly mating diploid population of effective size Ne. We have ascertained the e ect that ρ, the probability of transposon Modification during the developmental window, has on the population (species. One of our principal conclusions is that as ρ increases, the pattern of fixation of the combined TA locus goes from "neutral" to "dominant" to "over-dominant". We observe that, under realistic values of ρ, epigenetic Modifications can provide an e cient mechanism for more rapid fixation of transposons and cis-located gene alleles. The results obtained suggest that epigenetic silencing, even if strictly transient (being reset at each generation, can still have signi cant

  1. Epigenetics in mammary gland biology and cancer

    Science.gov (United States)

    In the post genome era, the focus has shifted to understanding the mechanisms that regulate the interpretation of the genetic code. "Epigenetics" as a research field is taking center stage. Epigenetics is a term which is now being used throughout the scientific community in different contexts from p...

  2. Epigenetic mechanisms in schizophrenia.

    Science.gov (United States)

    Akbarian, Schahram

    2014-09-01

    Schizophrenia is a major psychiatric disorder that lacks a unifying neuropathology, while currently available pharmacological treatments provide only limited benefits to many patients. This review will discuss how the field of neuroepigenetics could contribute to advancements of the existing knowledge on the neurobiology and treatment of psychosis. Genome-scale mapping of DMA methylation, histone modifications and variants, and chromosomal loopings for promoter-enhancer interactions and other epigenetic determinants of genome organization and function are likely to provide important clues about mechanisms contributing to dysregulated expression of synaptic and metabolic genes in schizophrenia brain, including the potential links to the underlying genetic risk architecture and environmental exposures. In addition, studies in animal models are providing a rapidly increasing list of chromatin-regulatory mechanisms with significant effects on cognition and complex behaviors, thereby pointing to the therapeutic potential of epigenetic drug targets in the nervous system.

  3. Theory of epigenetic coding.

    Science.gov (United States)

    Elder, D

    1984-06-07

    The logic of genetic control of development may be based on a binary epigenetic code. This paper revises the author's previous scheme dealing with the numerology of annelid metamerism in these terms. Certain features of the code had been deduced to be combinatorial, others not. This paradoxical contrast is resolved here by the interpretation that these features relate to different operations of the code; the combinatiorial to coding identity of units, the non-combinatorial to coding production of units. Consideration of a second paradox in the theory of epigenetic coding leads to a new solution which further provides a basis for epimorphic regeneration, and may in particular throw light on the "regeneration-duplication" phenomenon. A possible test of the model is also put forward.

  4. Epigenetic variation predicts regional and local intraspecific functional diversity in a perennial herb.

    Science.gov (United States)

    Medrano, Mónica; Herrera, Carlos M; Bazaga, Pilar

    2014-10-01

    The ecological significance of epigenetic variation has been generally inferred from studies on model plants under artificial conditions, but the importance of epigenetic differences between individuals as a source of intraspecific diversity in natural plant populations remains essentially unknown. This study investigates the relationship between epigenetic variation and functional plant diversity by conducting epigenetic (methylation-sensitive amplified fragment length polymorphisms, MSAP) and genetic (amplified fragment length polymorphisms, AFLP) marker-trait association analyses for 20 whole-plant, leaf and regenerative functional traits in a large sample of wild-growing plants of the perennial herb Helleborus foetidus from ten sampling sites in south-eastern Spain. Plants differed widely in functional characteristics, and exhibited greater epigenetic than genetic diversity, as shown by per cent polymorphism of MSAP fragments (92%) or markers (69%) greatly exceeding that for AFLP ones (41%). After controlling for genetic structuring and possible cryptic relatedness, every functional trait considered exhibited a significant association with at least one AFLP or MSAP marker. A total of 27 MSAP (13.0% of total) and 12 AFLP (4.4%) markers were involved in significant associations, which explained on average 8.2% and 8.0% of trait variance, respectively. Individual MSAP markers were more likely to be associated with functional traits than AFLP markers. Between-site differences in multivariate functional diversity were directly related to variation in multilocus epigenetic diversity after multilocus genetic diversity was statistically accounted for. Results suggest that epigenetic variation can be an important source of intraspecific functional diversity in H. foetidus, possibly endowing this species with the capacity to exploit a broad range of ecological conditions despite its modest genetic diversity. © 2014 John Wiley & Sons Ltd.

  5. Introduction to the Special Section on Epigenetics

    Science.gov (United States)

    Lester, Barry M.; Conradt, Elisabeth; Marsit, Carmen

    2016-01-01

    Epigenetics provides the opportunity to revolutionize our understanding of the role of genetics and the environment in explaining human behavior, although the use of epigenetics to study human behavior is just beginning. In this introduction, the authors present the basics of epigenetics in a way that is designed to make this exciting field…

  6. Directional Migration in Esophageal Squamous Cell Carcinoma (ESCC is Epigenetically Regulated by SET Nuclear Oncogene, a Member of the Inhibitor of Histone Acetyltransferase Complex

    Directory of Open Access Journals (Sweden)

    Xiang Yuan

    2017-11-01

    Full Text Available Directional cell migration is of fundamental importance to a variety of biological events, including metastasis of malignant cells. Herein, we specifically investigated SET oncoprotein, a subunit of the recently identified inhibitor of acetyltransferases (INHAT complex and identified its role in the establishment of front–rear cell polarity and directional migration in Esophageal Squamous Cell Carcinoma (ESCC. We further define the molecular circuits that govern these processes by showing that SET modulated DOCK7/RAC1 and cofilin signaling events. Moreover, a detailed analysis of the spatial distribution of RAC1 and cofilin allowed us to decipher the synergistical contributions of the two in coordinating the advancing dynamics by measuring architectures, polarities, and cytoskeletal organizations of the lamellipodia leading edges. In further investigations in vivo, we identified their unique role at multiple levels of the invasive cascade for SET cell and indicate the necessity for their functional balance to enable efficient invasion as well. Additionally, SET epigenetically repressed miR-30c expression by deacetylating histones H2B and H4 on its promoter, which was functionally important for the biological effects of SET in our cell-context. Finally, we corroborated our findings in vivo by evaluating the clinical relevance of SET signaling in the metastatic burden in mice and a large series of patients with ESCC at diagnosis, observing it's significance in predicting metastasis formation. Our findings uncovered a novel signaling network initiated by SET that epigenetically modulated ESCC properties and suggest that targeting the regulatory axis might be a promising strategy to inhibit migration and metastasis.

  7. Epigenetic regulation in Autism spectrum disorder

    Directory of Open Access Journals (Sweden)

    Sraboni Chaudhury

    2016-12-01

    Full Text Available Autism spectrum disorder (ASD is a neurodevelopmental disorder characterized by an impaired social communication skill and often results in repetitive, stereotyped behavior which is observed in children during the first few years of life. Other characteristic of this disorder includes language disabilities, difficulties in sensory integration, lack of reciprocal interactions and in some cases, cognitive delays. One percentage of the general population is affected by ASD and is four times more common in boys than girls. There are hundreds of genes, which has been identified to be associated with ASD etiology. However it remains difficult to comprehend our understanding in defining the genetic architecture necessary for complete exposition of its pathophysiology. Seeing the complexity of the disease, it is important to adopt a multidisciplinary approach which should not only focus on the “genetics” of autism but also on epigenetics, transcriptomics, immune system disruption and environmental factors that could all impact the pathogenesis of the disease. As environmental factors also play a key role in regulating the trigger of ASD, the role of chromatin remodeling and DNA methylation has started to emerge. Such epigenetic modifications directly link molecular regulatory pathways and environmental factors, which might be able to explain some aspects of complex disorders like ASD. The present review will focus on the role of epigenetic regulation in defining the underlying cause for ASD

  8. Epigenetic regulation in dental pulp inflammation

    Science.gov (United States)

    Hui, T; Wang, C; Chen, D; Zheng, L; Huang, D; Ye, L

    2016-01-01

    Dental caries, trauma, and other possible factors could lead to injury of the dental pulp. Dental infection could result in immune and inflammatory responses mediated by molecular and cellular events and tissue breakdown. The inflammatory response of dental pulp could be regulated by genetic and epigenetic events. Epigenetic modifications play a fundamental role in gene expression. The epigenetic events might play critical roles in the inflammatory process of dental pulp injury. Major epigenetic events include methylation and acetylation of histones and regulatory factors, DNA methylation, and small non-coding RNAs. Infections and other environmental factors have profound effects on epigenetic modifications and trigger diseases. Despite growing evidences of literatures addressing the role of epigenetics in the field of medicine and biology, very little is known about the epigenetic pathways involved in dental pulp inflammation. This review summarized the current knowledge about epigenetic mechanisms during dental pulp inflammation. Progress in studies of epigenetic alterations during inflammatory response would provide opportunities for the development of efficient medications of epigenetic therapy for pulpitis. PMID:26901577

  9. Using animal models to disentangle the role of genetic, epigenetic and environmental influences on behavioral outcomes associated with maternal anxiety and depression

    Directory of Open Access Journals (Sweden)

    Lisa M. Tarantino

    2011-07-01

    Full Text Available The etiology of complex psychiatric disorders results from both genetics and the environment. No definitive environmental factor has been implicated, but studies suggest that deficits in maternal care and bonding may be an important contributing factor in the development of anxiety and depression. Perinatal mood disorders such as postpartum depression (PPD occur in approximately 10% of pregnant women and can result in detriments in infant care and bonding. The consequences of impaired maternal-infant attachment during critical early brain development may lead to adverse effects on socioemotional and neurocognitive development in infants resulting in long-term behavioral and emotional problems, including increased vulnerability for mental illness. The exact mechanisms by which environmental stressors such as poor maternal care increase the risk for psychiatric disorders are not known and studies in humans have proven challenging. Two inbred mouse strains may prove useful for studying the interaction between maternal care and mood disorders. BALB/c (BALB mice are considered an anxious strain in comparison to C57BL/6 (B6 mice in behavioral models of anxiety. These strain differences are most often attributed to genetics but may also be due to environment and gene by environment interactions. For example, BALB mice are described as poor mothers and B6 mice as good mothers and mothering behavior in rodents has been reported to affect both anxiety and stress behaviors in offspring. Changes in gene methylation patterns in response to maternal care have also been reported, providing evidence for epigenetic mechanisms. Characterization of these two mouse inbred strains over the course of pregnancy and in the postpartum period for behavioral and neuroendocrine changes may provide useful information by which to inform human studies, leading to advances in our understanding of the etiology of anxiety and depression and the role of genetics and the

  10. The Emerging Role of Epigenetics in Inflammation and Immunometabolism

    DEFF Research Database (Denmark)

    Raghuraman, Sukanya; Donkin, Ida; Versteyhe, Soetkin

    2016-01-01

    Recent research developments have shed light on the risk factors contributing to metabolic complications, implicating both genetic and environmental factors, potentially integrated by epigenetic mechanisms. Distinct epigenetic changes in immune cells are frequently observed in obesity and type 2 ...... we provide an overview of the epigenetic mechanisms influencing immune cell phenotype and function, summarize current knowledge about epigenetic changes affecting immune functions in the context of metabolic diseases, and discuss the therapeutic options currently available to counteract...

  11. [Nutritional epigenetics and epigenetic effects of human breast milk].

    Science.gov (United States)

    Lukoyanova, O L; Borovik, T E

    The article provides an overview of the current literature on nutritional epigenetics. There are currently actively studied hypothesis that nutrition especially in early life or in critical periods of the development, may have a role in modulating gene expression, and, therefore, have later effects on health in adults. Nutritional epigenetics concerns knowledge about the possible effects of nutrients on gene expression. Human breast milk is well-known for its ability in preventing necrotizing enterocolitis, infectious diseases, and also non-communicable diseases, such as obesity and related disorders. This paper discusses about presumed epigenetic effects of human breast milk and some its components. While evidence suggests that a direct relationship may exist of some components of human breast milk with epigenetic changes, the mechanisms involved are stillunclear.

  12. Epigenetic variation, phenotypic heritability, and evolution

    DEFF Research Database (Denmark)

    Furrow, Robert E.; Christiansen, Freddy Bugge; Feldman, Marcus W.

    2014-01-01

    families. The potential importance of this interaction, recognized in classical studies of the genetic epidemiology of complex diseases and other quantitative characters, has reemerged in studies of the effects of epigenetic modifications, their variation, and their transmission between generations....

  13. [Direct to consumer genetic testing: is it the moment?].

    Science.gov (United States)

    Lamoril, Jérôme; Bogard, Marc

    2016-01-01

    Since the development of new human genome sequencing technologies at the beginning of the 2000, commercial companies have developped direct to consumer genomic services, which means without medical prescription. From 2007 to 2013, many companies have offered services assesing associated risk with human public health in the world especially in the United States. This kind of company is forbidden in France. From 2009 to 2013, in United States, under the pressure of national or state health administrations, these companies have been progressively forbidden. However, in certain parts of the world, companies are still offering such services. The latter raise many different questions such as ethical, juridical, medical, scientific, educative, professional one. Many studies and debates have demonstrated their limit and the lack of usefulness and advantage in the field of human health for the time being. The commercialization of this type of services has arrived all too soon et is not yet ripe. In our time of globalization, with the lack of international rules controlling direct access to genetic services in the field of human health, there is an urgent need to regulate. International administrations and politicians must act fast. Inevitably, under the pressure of lobbies and citizens, companies (multinational or not) will develop especially as 1) new sequencing technologies evolve rapidly, 2) are cheaper from year to year, 3) scientific and medical knowledges are progressing quickly, 4) services are spreading faster through the web and other networks.

  14. Direct and maternal genetic effects for birth weight in dorper and ...

    African Journals Online (AJOL)

    Variance components for birth (BWT) in Dorper and Mutton Merino sheep were estimated by Average Information Restricted Maximum Likelihood (AIREML). Animal model was fitted allowing for genetic maternal effects and a genetic covariance between direct and maternal effects. Estimates of heritability for direct genetic ...

  15. Clinical Practice: Direct-to-consumer genetic testing: To test or not to ...

    African Journals Online (AJOL)

    In direct-to-consumer (DTC) genetic testing, laboratory-based genetic services are offered directly to the public without an independent healthcare professional being involved. The committee of the Southern African Society for Human Genetics (SASHG) appeals to the public and clinicians to be cautious when considering ...

  16. Effect of Maternal Diabetes on the Embryo, Fetus, and Children: Congenital Anomalies, Genetic and Epigenetic Changes and Developmental Outcomes

    Czech Academy of Sciences Publication Activity Database

    Ornoy, A.; Reece, E.A.; Pavlínková, Gabriela; Kappen, C.; Miller, R.K.

    2015-01-01

    Roč. 105, č. 1 (2015), s. 53-72 ISSN 1542-975X R&D Projects: GA MŠk(CZ) ED1.1.00/02.0109 Institutional research plan: CEZ:AV0Z50520701 Keywords : PGDM * GDM * congenital anomalies Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.120, year: 2015

  17. Prostate cancer epigenetics and its clinical implications.

    Science.gov (United States)

    Yegnasubramanian, Srinivasan

    2016-01-01

    Normal cells have a level of epigenetic programming that is superimposed on the genetic code to establish and maintain their cell identity and phenotypes. This epigenetic programming can be thought as the architecture, a sort of cityscape, that is built upon the underlying genetic landscape. The epigenetic programming is encoded by a complex set of chemical marks on DNA, on histone proteins in nucleosomes, and by numerous context-specific DNA, RNA, protein interactions that all regulate the structure, organization, and function of the genome in a given cell. It is becoming increasingly evident that abnormalities in both the genetic landscape and epigenetic cityscape can cooperate to drive carcinogenesis and disease progression. Large-scale cancer genome sequencing studies have revealed that mutations in genes encoding the enzymatic machinery for shaping the epigenetic cityscape are among the most common mutations observed in human cancers, including prostate cancer. Interestingly, although the constellation of genetic mutations in a given cancer can be quite heterogeneous from person to person, there are numerous epigenetic alterations that appear to be highly recurrent, and nearly universal in a given cancer type, including in prostate cancer. The highly recurrent nature of these alterations can be exploited for development of biomarkers for cancer detection and risk stratification and as targets for therapeutic intervention. Here, we explore the basic principles of epigenetic processes in normal cells and prostate cancer cells and discuss the potential clinical implications with regards to prostate cancer biomarker development and therapy.

  18. Prostate cancer epigenetics and its clinical implications

    Directory of Open Access Journals (Sweden)

    Srinivasan Yegnasubramanian

    2016-01-01

    Full Text Available Normal cells have a level of epigenetic programming that is superimposed on the genetic code to establish and maintain their cell identity and phenotypes. This epigenetic programming can be thought as the architecture, a sort of cityscape, that is built upon the underlying genetic landscape. The epigenetic programming is encoded by a complex set of chemical marks on DNA, on histone proteins in nucleosomes, and by numerous context-specific DNA, RNA, protein interactions that all regulate the structure, organization, and function of the genome in a given cell. It is becoming increasingly evident that abnormalities in both the genetic landscape and epigenetic cityscape can cooperate to drive carcinogenesis and disease progression. Large-scale cancer genome sequencing studies have revealed that mutations in genes encoding the enzymatic machinery for shaping the epigenetic cityscape are among the most common mutations observed in human cancers, including prostate cancer. Interestingly, although the constellation of genetic mutations in a given cancer can be quite heterogeneous from person to person, there are numerous epigenetic alterations that appear to be highly recurrent, and nearly universal in a given cancer type, including in prostate cancer. The highly recurrent nature of these alterations can be exploited for development of biomarkers for cancer detection and risk stratification and as targets for therapeutic intervention. Here, we explore the basic principles of epigenetic processes in normal cells and prostate cancer cells and discuss the potential clinical implications with regards to prostate cancer biomarker development and therapy.

  19. Nice to meet you: genetic, epigenetic and metabolic controls of plant perception of beneficial associative and endophytic diazotrophic bacteria in non-leguminous plants.

    Science.gov (United States)

    Carvalho, T L G; Ballesteros, H G F; Thiebaut, F; Ferreira, P C G; Hemerly, A S

    2016-04-01

    A wide range of rhizosphere diazotrophic bacteria are able to establish beneficial associations with plants, being able to associate to root surfaces or even endophytically colonize plant tissues. In common, both associative and endophytic types of colonization can result in beneficial outcomes to the plant leading to plant growth promotion, as well as increase in tolerance against biotic and abiotic stresses. An intriguing question in such associations is how plant cell surface perceives signals from other living organisms, thus sorting pathogens from beneficial ones, to transduce this information and activate proper responses that will finally culminate in plant adaptations to optimize their growth rates. This review focuses on the recent advances in the understanding of genetic and epigenetic controls of plant-bacteria signaling and recognition during beneficial associations with associative and endophytic diazotrophic bacteria. Finally, we propose that "soil-rhizosphere-rhizoplane-endophytes-plant" could be considered as a single coordinated unit with dynamic components that integrate the plant with the environment to generate adaptive responses in plants to improve growth. The homeostasis of the whole system should recruit different levels of regulation, and recognition between the parties in a given environment might be one of the crucial factors coordinating these adaptive plant responses.

  20. [Scientific potential of phenomics - functional direction of genetics].

    Science.gov (United States)

    Marasanov, A V; Valtseva, E A

    In this paper on the based on the integration of known theories, doctrines and concepts - principles of consistency and self-regulation of physiological functions (Pavlov I.P., 1950), the theory offunctional systems (Anokhin P.K., 1973), the theory of adaptive reactions (Selye H., 1960 ; Garkavi LKh et al, 1979), the doctrine of the dominant (Ukhtomsky A.A., 1966), doctrine on health (Baevsky R.M.), doctrine on the body type of the human by Merlin VS. conception on the “the interrelationship between the function and genetic apparatus” by Meyerson F.Z., Pshennikova M.G., Platonov V.N., and others, there is proposed to select phenomics - functional division of genetics considering the poolability of specific mechanisms of the body in an integral system of the adaptive act in favor of the development of a personalized approach to the diagnosis and prevention of non-communicable diseases, increasing life expectancy of working age into the particular scientific direction. The task of phenomics is the establishment of the phenotypic characteristics of the person, norms of the response of systems of his body, determination of the deviation of the level of the functioning of the each system from the norm of its response and the elaboration of the tactics for the correction of the functional state of the organism (the optimization of its life activity), with taking into account the directedness of the interaction of body systems. The description of the shaping of the mechanism of stereotyped response of the organism generated an important contribution to the development of phenomics. Stereotyped response being initiated by the non-specific response of the body is aimed at the shaping of the activity of its systems after a fashion of norms of the activity, promotes the recovery of the specificity of the body, plays an important role in the establishment of cause-effect relations of the disease.

  1. Transposable elements, a treasure trove to decipher epigenetic variation: insights from Arabidopsis and crop epigenomes.

    Science.gov (United States)

    Mirouze, Marie; Vitte, Clémentine

    2014-06-01

    In the past decade, plant biologists and breeders have developed a growing interest in the field of epigenetics, which is defined as the study of heritable changes in gene expression that cannot be explained by changes in the DNA sequence. Epigenetic marks can be responsive to the environment, and evolve faster than genetic changes. Therefore, epigenetic diversity may represent an unexplored resource of natural variation that could be used in plant breeding programmes. On the other hand, crop genomes are largely populated with transposable elements (TEs) that are efficiently targeted by epigenetic marks, and part of the epigenetic diversity observed might be explained by TE polymorphisms. Characterizing the degree to which TEs influence epigenetic variation in crops is therefore a major goal to better use epigenetic variation. To date, epigenetic analyses have been mainly focused on the model plant Arabidopsis thaliana, and have provided clues on epigenome features, components that silence pathways, and effects of silencing impairment. But to what extent can Arabidopsis be used as a model for the epigenomics of crops? In this review, we discuss the similarities and differences between the epigenomes of Arabidopsis and crops. We explore the relationship between TEs and epigenomes, focusing on TE silencing control and escape, and the impact of TE mobility on epigenomic variation. Finally, we provide insights into challenges to tackle, and future directions to take in the route towards using epigenetic diversity in plant breeding programmes. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  2. Epigenetic Etiology of Intellectual Disability.

    Science.gov (United States)

    Iwase, Shigeki; Bérubé, Nathalie G; Zhou, Zhaolan; Kasri, Nael Nadif; Battaglioli, Elena; Scandaglia, Marilyn; Barco, Angel

    2017-11-08

    Intellectual disability (ID) is a prevailing neurodevelopmental condition associated with impaired cognitive and adaptive behaviors. Many chromatin-modifying enzymes and other epigenetic regulators have been genetically associated with ID disorders (IDDs). Here we review how alterations in the function of histone modifiers, chromatin remodelers, and methyl-DNA binding proteins contribute to neurodevelopmental defects and altered brain plasticity. We also discuss how progress in human genetics has led to the generation of mouse models that unveil the molecular etiology of ID, and outline the direction in which this field is moving to identify therapeutic strategies for IDDs. Importantly, because the chromatin regulators linked to IDDs often target common downstream genes and cellular processes, the impact of research in individual syndromes goes well beyond each syndrome and can also contribute to the understanding and therapy of other IDDs. Furthermore, the investigation of these disorders helps us to understand the role of chromatin regulators in brain development, plasticity, and gene expression, thereby answering fundamental questions in neurobiology. Copyright © 2017 the authors 0270-6474/17/3710773-10$15.00/0.

  3. Introduction to the Special Section on Epigenetics.

    Science.gov (United States)

    Lester, Barry M; Conradt, Elisabeth; Marsit, Carmen

    2016-01-01

    Epigenetics provides the opportunity to revolutionize our understanding of the role of genetics and the environment in explaining human behavior, although the use of epigenetics to study human behavior is just beginning. In this introduction, the authors present the basics of epigenetics in a way that is designed to make this exciting field accessible to a wide readership. The authors describe the history of human behavioral epigenetic research in the context of other disciplines and graphically illustrate the burgeoning of research in the application of epigenetic methods and principles to the study of human behavior. The role of epigenetics in normal embryonic development and the influence of biological and environmental factors altering behavior through epigenetic mechanisms and developmental programming are discussed. Some basic approaches to the study of epigenetics are reviewed. The authors conclude with a discussion of challenges and opportunities, including intervention, as the field of human behavioral epigenetics continue to grow. © 2016 The Authors. Child Development © 2016 Society for Research in Child Development, Inc.

  4. Epigenetic changes detected in micropropagated hop plants.

    Science.gov (United States)

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

    2009-07-01

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

  5. [Epigenetics of schizophrenia: a review].

    Science.gov (United States)

    Rivollier, F; Lotersztajn, L; Chaumette, B; Krebs, M-O; Kebir, O

    2014-10-01

    Schizophrenia is a frequent and disabling disease associated with heterogeneous psychiatric phenotypes. It emerges during childhood, adolescence or young adulthood and has dramatic consequences for the affected individuals, causing considerable familial and social burden, as well as increasing health expenses. Although some progress has been made in the understanding of their physiopathology, many questions remain unsolved, and the disease is still poorly understood. The prevailing hypothesis regarding psychotic disorders proposes that a combination of genetic and/or environmental factors, during critical periods of brain development increases the risk for these illnesses. Epigenetic regulations, such as DNA methylation, can mediate gene x environment interactions at the level of the genome and may provide a potential substrate to explain the variability in symptom severity and family heritability. Initially, epigenetics was used to design mitotic and meiotic changes in gene transcription that could not be attributed to genetic mutations. It referred later to changes in the epigenome not transmitted through the germline. Thus, epigenetics refers to a wide range of molecular mechanisms including DNA methylation of cytosine residues in CpG dinucleotides and post-translational histone modifications. These mechanisms alter the way the transcriptional factors bind the DNA, modulating its expression. Prenatal and postnatal environmental factors may affect these epigenetics factors, having responsability in long-term DNA transcription, and influencing the development of psychiatric disorders. The object of this review is to present the state of knowledge in epigenetics of schizophrenia, outlining the most recent findings in the matter. We did so using Pubmed, researching words such as 'epigenetics', 'epigenetic', 'schizophrenia', 'psychosis', 'psychiatric'. This review summarizes evidences mostly for two epigenetic mechanisms: DNA methylation and post

  6. Dual gene activation and knockout screen reveals directional dependencies in genetic networks. | Office of Cancer Genomics

    Science.gov (United States)

    Understanding the direction of information flow is essential for characterizing how genetic networks affect phenotypes. However, methods to find genetic interactions largely fail to reveal directional dependencies. We combine two orthogonal Cas9 proteins from Streptococcus pyogenes and Staphylococcus aureus to carry out a dual screen in which one gene is activated while a second gene is deleted in the same cell. We analyze the quantitative effects of activation and knockout to calculate genetic interaction and directionality scores for each gene pair.

  7. Epigenetic Effect of Environmental Factors on Autism Spectrum Disorders

    Directory of Open Access Journals (Sweden)

    Takeo Kubota

    2016-05-01

    Full Text Available Both environmental factors and genetic factors are involved in the pathogenesis of autism spectrum disorders (ASDs. Epigenetics, an essential mechanism for gene regulation based on chemical modifications of DNA and histone proteins, is also involved in congenital ASDs. It was recently demonstrated that environmental factors, such as endocrine disrupting chemicals and mental stress in early life, can change epigenetic status and gene expression, and can cause ASDs. Moreover, environmentally induced epigenetic changes are not erased during gametogenesis and are transmitted to subsequent generations, leading to changes in behavior phenotypes. However, epigenetics has a reversible nature since it is based on the addition or removal of chemical residues, and thus the original epigenetic status may be restored. Indeed, several antidepressants and anticonvulsants used for mental disorders including ASDs restore the epigenetic state and gene expression. Therefore, further epigenetic understanding of ASDs is important for the development of new drugs that take advantages of epigenetic reversibility.

  8. Epigenetic Effect of Environmental Factors on Autism Spectrum Disorders.

    Science.gov (United States)

    Kubota, Takeo; Mochizuki, Kazuki

    2016-05-14

    Both environmental factors and genetic factors are involved in the pathogenesis of autism spectrum disorders (ASDs). Epigenetics, an essential mechanism for gene regulation based on chemical modifications of DNA and histone proteins, is also involved in congenital ASDs. It was recently demonstrated that environmental factors, such as endocrine disrupting chemicals and mental stress in early life, can change epigenetic status and gene expression, and can cause ASDs. Moreover, environmentally induced epigenetic changes are not erased during gametogenesis and are transmitted to subsequent generations, leading to changes in behavior phenotypes. However, epigenetics has a reversible nature since it is based on the addition or removal of chemical residues, and thus the original epigenetic status may be restored. Indeed, several antidepressants and anticonvulsants used for mental disorders including ASDs restore the epigenetic state and gene expression. Therefore, further epigenetic understanding of ASDs is important for the development of new drugs that take advantages of epigenetic reversibility.

  9. Directed genetic modification of African horse sickness virus by reverse genetics

    Directory of Open Access Journals (Sweden)

    Elaine Vermaak

    2015-07-01

    Full Text Available African horse sickness virus (AHSV, a member of the Orbivirus genus in the family Reoviridae, is an arthropod-transmitted pathogen that causes a devastating disease in horses with a mortality rate greater than 90%. Fundamental research on AHSV and the development of safe, efficacious vaccines could benefit greatly from an uncomplicated genetic modification method to generate recombinant AHSV. We demonstrate that infectious AHSV can be recovered by transfection of permissive mammalian cells with transcripts derived in vitro from purified AHSV core particles. These findings were expanded to establish a genetic modification system for AHSV that is based on transfection of the cells with a mixture of purified core transcripts and a synthetic T7 transcript. This approach was applied successfully to recover a directed cross-serotype reassortant AHSV and to introduce a marker sequence into the viral genome. The ability to manipulate the AHSV genome and engineer specific mutants will increase understanding of AHSV replication and pathogenicity, as well as provide a tool for generating designer vaccine strains.

  10. Epigenetics and Colorectal Cancer Pathogenesis

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    Bardhan, Kankana; Liu, Kebin, E-mail: Kliu@gru.edu [Department of Biochemistry and Molecular Biology, Medical College of Georgia, and Cancer Center, Georgia Regents University, Augusta, GA 30912 (United States)

    2013-06-05

    Colorectal cancer (CRC) develops through a multistage process that results from the progressive accumulation of genetic mutations, and frequently as a result of mutations in the Wnt signaling pathway. However, it has become evident over the past two decades that epigenetic alterations of the chromatin, particularly the chromatin components in the promoter regions of tumor suppressors and oncogenes, play key roles in CRC pathogenesis. Epigenetic regulation is organized at multiple levels, involving primarily DNA methylation and selective histone modifications in cancer cells. Assessment of the CRC epigenome has revealed that virtually all CRCs have aberrantly methylated genes and that the average CRC methylome has thousands of abnormally methylated genes. Although relatively less is known about the patterns of specific histone modifications in CRC, selective histone modifications and resultant chromatin conformation have been shown to act, in concert with DNA methylation, to regulate gene expression to mediate CRC pathogenesis. Moreover, it is now clear that not only DNA methylation but also histone modifications are reversible processes. The increased understanding of epigenetic regulation of gene expression in the context of CRC pathogenesis has led to development of epigenetic biomarkers for CRC diagnosis and epigenetic drugs for CRC therapy.

  11. Epigenetics and colorectal cancer pathogenesis.

    Science.gov (United States)

    Bardhan, Kankana; Liu, Kebin

    2013-06-05

    Colorectal cancer (CRC) develops through a multistage process that results from the progressive accumulation of genetic mutations, and frequently as a result of mutations in the Wnt signaling pathway. However, it has become evident over the past two decades that epigenetic alterations of the chromatin, particularly the chromatin components in the promoter regions of tumor suppressors and oncogenes, play key roles in CRC pathogenesis. Epigenetic regulation is organized at multiple levels, involving primarily DNA methylation and selective histone modifications in cancer cells. Assessment of the CRC epigenome has revealed that virtually all CRCs have aberrantly methylated genes and that the average CRC methylome has thousands of abnormally methylated genes. Although relatively less is known about the patterns of specific histone modifications in CRC, selective histone modifications and resultant chromatin conformation have been shown to act, in concert with DNA methylation, to regulate gene expression to mediate CRC pathogenesis. Moreover, it is now clear that not only DNA methylation but also histone modifications are reversible processes. The increased understanding of epigenetic regulation of gene expression in the context of CRC pathogenesis has led to development of epigenetic biomarkers for CRC diagnosis and epigenetic drugs for CRC therapy.

  12. Epigenetics and Colorectal Cancer Pathogenesis

    International Nuclear Information System (INIS)

    Bardhan, Kankana; Liu, Kebin

    2013-01-01

    Colorectal cancer (CRC) develops through a multistage process that results from the progressive accumulation of genetic mutations, and frequently as a result of mutations in the Wnt signaling pathway. However, it has become evident over the past two decades that epigenetic alterations of the chromatin, particularly the chromatin components in the promoter regions of tumor suppressors and oncogenes, play key roles in CRC pathogenesis. Epigenetic regulation is organized at multiple levels, involving primarily DNA methylation and selective histone modifications in cancer cells. Assessment of the CRC epigenome has revealed that virtually all CRCs have aberrantly methylated genes and that the average CRC methylome has thousands of abnormally methylated genes. Although relatively less is known about the patterns of specific histone modifications in CRC, selective histone modifications and resultant chromatin conformation have been shown to act, in concert with DNA methylation, to regulate gene expression to mediate CRC pathogenesis. Moreover, it is now clear that not only DNA methylation but also histone modifications are reversible processes. The increased understanding of epigenetic regulation of gene expression in the context of CRC pathogenesis has led to development of epigenetic biomarkers for CRC diagnosis and epigenetic drugs for CRC therapy

  13. Epigenetics and Colorectal Cancer Pathogenesis

    Directory of Open Access Journals (Sweden)

    Kebin Liu

    2013-06-01

    Full Text Available Colorectal cancer (CRC develops through a multistage process that results from the progressive accumulation of genetic mutations, and frequently as a result of mutations in the Wnt signaling pathway. However, it has become evident over the past two decades that epigenetic alterations of the chromatin, particularly the chromatin components in the promoter regions of tumor suppressors and oncogenes, play key roles in CRC pathogenesis. Epigenetic regulation is organized at multiple levels, involving primarily DNA methylation and selective histone modifications in cancer cells. Assessment of the CRC epigenome has revealed that virtually all CRCs have aberrantly methylated genes and that the average CRC methylome has thousands of abnormally methylated genes. Although relatively less is known about the patterns of specific histone modifications in CRC, selective histone modifications and resultant chromatin conformation have been shown to act, in concert with DNA methylation, to regulate gene expression to mediate CRC pathogenesis. Moreover, it is now clear that not only DNA methylation but also histone modifications are reversible processes. The increased understanding of epigenetic regulation of gene expression in the context of CRC pathogenesis has led to development of epigenetic biomarkers for CRC diagnosis and epigenetic drugs for CRC therapy.

  14. Epigenetic effects of ionizing radiation

    International Nuclear Information System (INIS)

    EI-Naggar, A.M.

    2007-01-01

    Data generated during the last three decades provide evidence of Epigenetic Effects that ave-induced by ionizing radiation, particularly those of high LET values, and low level dose exposures. Epigenesist is defined as the stepwise process by which genetic information, as modified by environmental influences, is translated into the substance and behavior of cells, tissues, organism.The epigenetic effects cited in the literature are essentially classified into fine types depending on the type and nature of the effect induced.The most accepted postulation, for the occurrence of these epigenetic effects, is a radiation induced bio electric disturbances in the environment of the non-irradiated cellular volume. This will trigger signals that will induce effects in the unirradiated cells.The epigenetic effects referenced in the literature up to date are five types; namely, Genomic Instability, Bystander. Effects, Clastogenic Plasma Factors,, Abscopal Effects, and Tran generational Effects.The demonstration of Epigenetic Effects associated with exposure to ionizing radiation indicates the need to re- examine the concept of radiation dose and target size. Also an improved understanding of qualifiring and quantifying radiation risk estimates may be attained. Also, a more logical means to understand the underlying mechanisms of radiation induced carcinogenic transformation of cells

  15. Daphnia as an Emerging Epigenetic Model Organism

    Directory of Open Access Journals (Sweden)

    Kami D. M. Harris

    2012-01-01

    Full Text Available Daphnia offer a variety of benefits for the study of epigenetics. Daphnia’s parthenogenetic life cycle allows the study of epigenetic effects in the absence of confounding genetic differences. Sex determination and sexual reproduction are epigenetically determined as are several other well-studied alternate phenotypes that arise in response to environmental stressors. Additionally, there is a large body of ecological literature available, recently complemented by the genome sequence of one species and transgenic technology. DNA methylation has been shown to be altered in response to toxicants and heavy metals, although investigation of other epigenetic mechanisms is only beginning. More thorough studies on DNA methylation as well as investigation of histone modifications and RNAi in sex determination and predator-induced defenses using this ecologically and evolutionarily important organism will contribute to our understanding of epigenetics.

  16. Mining literature for a comprehensive pathway analysis: A case study for retrieval of homocysteine related genes for genetic and epigenetic studies

    Directory of Open Access Journals (Sweden)

    Mahajan Anubha

    2006-01-01

    Full Text Available Abstract Homocysteine is an independent risk factor for cardiovascular diseases. It is also known to be associated with a variety of complex disorders. While there are a large number of independent studies implicating homocysteine in isolated pathways, the mechanism of homocysteine induced adverse effects are not clear. Homocysteine-induced modulation of gene expression through alteration of methylation status or by hitherto unknown mechanisms is predicted to lead to several pathological conditions either directly or indirectly. In the present manuscript, using literature mining approach, we have identified the genes that are modulated directly or indirectly by an elevated level of homocysteine. These genes were then placed in appropriate pathways in an attempt to understand the molecular basis of homocysteine induced complex disorders and to provide a resource for selection of genes for polymorphism screening and analysis of mutations as well as epigenetic modifications in relation to hyperhomocysteinemia. We have identified 135 genes in 1137 abstracts that either modulate the levels of homocysteine or are modulated by elevated levels of homocysteine. Mapping the genes to their respective pathways revealed that an elevated level of homocysteine leads to the atherosclerosis either by directly affecting lipid metabolism and transport or via oxidative stress and/or Endoplasmic Reticulum (ER stress. Elevated levels of homocysteine also decreases the bioavailability of nitric oxide and modulates the levels of other metabolites including S-adenosyl methionine and S-adenosyl homocysteine which may result in cardiovascular or neurological disorders. The ER stress emerges as the common pathway that relates to apoptosis, atherosclerosis and neurological disorders and is modulated by levels of homocysteine. The comprehensive network collated has lead to the identification of genes that are modulated by homocysteine indicating that homocysteine exerts its

  17. ACOG Committee Opinion No. 409: Direct-to-consumer marketing of genetic testing.

    Science.gov (United States)

    2008-06-01

    Marketing of genetic testing, although similar to direct-to-consumer advertising of prescription drugs, raises additional concerns and considerations. These include issues of limited knowledge among patients and health care providers of available genetic tests, difficulty in interpretation of genetic testing results, lack of federal oversight of companies offering genetic testing, and issues of privacy and confidentiality. Until all of these considerations are addressed, direct or home genetic testing should be discouraged because of the potential harm of a misinterpreted or inaccurate result.

  18. Epigenetics of obesity: beyond the genome sequence.

    Science.gov (United States)

    Cordero, Paul; Li, Jiawei; Oben, Jude A

    2015-07-01

    After the study of the gene code as a trigger for obesity, epigenetic code has appeared as a novel tool in the diagnosis, prognosis and treatment of obesity, and its related comorbidities. This review summarizes the status of the epigenetic field associated with obesity, and the current epigenetic-based approaches for obesity treatment. Thanks to technical advances, novel and key obesity-associated polymorphisms have been described by genome-wide association studies, but there are limitations with their predictive power. Epigenetics is also studied for disease association, which involves decoding of the genome information, transcriptional status and later phenotypes. Obesity could be induced during adult life by feeding and other environmental factors, and there is a strong association between obesity features and specific epigenetic patterns. These patterns could be established during early life stages, and programme the risk of obesity and its comorbidities during adult life. Furthermore, recent studies have shown that DNA methylation profile could be applied as biomarkers of diet-induced weight loss treatment. High-throughput technologies, recently implemented for commercial genetic test panels, could soon lead to the creation of epigenetic test panels for obesity. Nonetheless, epigenetics is a modifiable risk factor, and different dietary patterns or environmental insights during distinct stages of life could lead to rewriting of the epigenetic profile.

  19. The multifaceted interplay between lipids and epigenetics.

    Science.gov (United States)

    Dekkers, Koen F; Slagboom, P Eline; Jukema, J Wouter; Heijmans, Bastiaan T

    2016-06-01

    The interplay between lipids and epigenetic mechanisms has recently gained increased interest because of its relevance for common diseases and most notably atherosclerosis. This review discusses recent advances in unravelling this interplay with a particular focus on promising approaches and methods that will be able to establish causal relationships. Complementary approaches uncovered close links between circulating lipids and epigenetic mechanisms at multiple levels. A characterization of lipid-associated genetic variants suggests that these variants exert their influence on lipid levels through epigenetic changes in the liver. Moreover, exposure of monocytes to lipids persistently alters their epigenetic makeup resulting in more proinflammatory cells. Hence, epigenetic changes can both impact on and be induced by lipids. It is the combined application of technological advances to probe epigenetic modifications at a genome-wide scale and methodological advances aimed at causal inference (including Mendelian randomization and integrative genomics) that will elucidate the interplay between circulating lipids and epigenetics. Understanding its role in the development of atherosclerosis holds the promise of identifying a new category of therapeutic targets, since epigenetic changes are amenable to reversal.

  20. Epigenetic Pathways of Oncogenic Viruses: Therapeutic Promises.

    Science.gov (United States)

    El-Araby, Amr M; Fouad, Abdelrahman A; Hanbal, Amr M; Abdelwahab, Sara M; Qassem, Omar M; El-Araby, Moustafa E

    2016-02-01

    Cancerous transformation comprises different events that are both genetic and epigenetic. The ultimate goal for such events is to maintain cell survival and proliferation. This transformation occurs as a consequence of different features such as environmental and genetic factors, as well as some types of infection. Many viral infections are considered to be causative agents of a number of different malignancies. To convert normal cells into cancerous cells, oncogenic viruses must function at the epigenetic level to communicate with their host cells. Oncogenic viruses encode certain epigenetic factors that lead to the immortality and proliferation of infected cells. The epigenetic effectors produced by oncogenic viruses constitute appealing targets to prevent and treat malignant diseases caused by these viruses. In this review, we highlight the importance of epigenetic reprogramming for virus-induced oncogenesis, with special emphasis on viral epigenetic oncoproteins as therapeutic targets. The discovery of molecular components that target epigenetic pathways, especially viral factors, is also discussed. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Understanding Neurological Disease Mechanisms in the Era of Epigenetics

    Science.gov (United States)

    Qureshi, Irfan A.; Mehler, Mark F.

    2015-01-01

    The burgeoning field of epigenetics is making a significant impact on our understanding of brain evolution, development, and function. In fact, it is now clear that epigenetic mechanisms promote seminal neurobiological processes, ranging from neural stem cell maintenance and differentiation to learning and memory. At the molecular level, epigenetic mechanisms regulate the structure and activity of the genome in response to intracellular and environmental cues, including the deployment of cell type–specific gene networks and those underlying synaptic plasticity. Pharmacological and genetic manipulation of epigenetic factors can, in turn, induce remarkable changes in neural cell identity and cognitive and behavioral phenotypes. Not surprisingly, it is also becoming apparent that epigenetics is intimately involved in neurological disease pathogenesis. Herein, we highlight emerging paradigms for linking epigenetic machinery and processes with neurological disease states, including how (1) mutations in genes encoding epigenetic factors cause disease, (2) genetic variation in genes encoding epigenetic factors modify disease risk, (3) abnormalities in epigenetic factor expression, localization, or function are involved in disease pathophysiology, (4) epigenetic mechanisms regulate disease-associated genomic loci, gene products, and cellular pathways, and (5) differential epigenetic profiles are present in patient-derived central and peripheral tissues. PMID:23571666

  2. The epigenetic footprint of poleward range-expanding plants in apomictic dandelions

    NARCIS (Netherlands)

    Preite, V.; Snoek, L.B.; Oplaat, C.; Biere, A.; Putten, van der W.H.; Verhoeven, K.J.F.

    2015-01-01

    Epigenetic modifications, such as DNA methylation variation, can generate heritable phenotypic variation independent of the underlying genetic code. However, epigenetic variation in natural plant populations is poorly documented and little understood. Here, we test if northward range expansion of

  3. Imaging epigenetics in Alzheimer's disease.

    Science.gov (United States)

    Lista, Simone; Garaci, Francesco G; Toschi, Nicola; Hampel, Harald

    2013-01-01

    Sporadic Alzheimer's disease (AD) is a prevalent, complex and chronically progressive brain disease. Its course is non-linear, dynamic, adaptive to maladaptive, and compensatory to decompensatory, affecting large-scale neural networks through a plethora of mechanistic and signaling pathway alterations that converge into regional and cell type-specific neurodegeneration and, finally, into clinically overt cognitive and behavioral decline. This decline includes reductions in the activities of daily living, quality of life, independence, and life expectancy. Evolving lines of research suggest that epigenetic mechanisms may play a crucial role during AD development and progression. Epigenetics designates molecular mechanisms that alter gene expression without modifications of the genetic code. This topic includes modifications on DNA and histone proteins, the primary elements of chromatin structure. Accumulating evidence has revealed the relevant processes that mediate epigenetic modifications and has begun to elucidate how these processes are apparently dysregulated in AD. This evidence has led to the clarification of the roles of specific classes of therapeutic compounds that affect epigenetic pathways and characteristics of the epigenome. This insight is accompanied by the development of new methods for studying the global patterns of DNA methylation and chromatin alterations. In particular, high-throughput sequencing approaches, such as next-generation DNA sequencing techniques, are beginning to drive the field into the next stage of development. In parallel, genetic imaging is beginning to answer additional questions through its ability to uncover genetic variants, with or without genome-wide significance, that are related to brain structure, function and metabolism, which impact disease risk and fundamental network-based cognitive processes. Neuroimaging measures can further be used to define AD systems and endophenotypes. The integration of genetic neuroimaging

  4. Epigenetics: general characteristics and implications for oral health

    Directory of Open Access Journals (Sweden)

    Ji-Yun Seo

    2015-02-01

    Full Text Available Genetic information such as DNA sequences has been limited to fully explain mechanisms of gene regulation and disease process. Epigenetic mechanisms, which include DNA methylation, histone modification and non-coding RNAs, can regulate gene expression and affect progression of disease. Although studies focused on epigenetics are being actively investigated in the field of medicine and biology, epigenetics in dental research is at the early stages. However, studies on epigenetics in dentistry deserve attention because epigenetic mechanisms play important roles in gene expression during tooth development and may affect oral diseases. In addition, understanding of epigenetic alteration is important for developing new therapeutic methods. This review article aims to outline the general features of epigenetic mechanisms and describe its future implications in the field of dentistry.

  5. Evolution, epigenetics and cooperation.

    Science.gov (United States)

    Bateson, Patrick

    2014-04-01

    Explanations for biological evolution in terms of changes in gene frequencies refer to outcomes rather than process. Integrating epigenetic studies with older evolutionary theories has drawn attention to the ways in which evolution occurs. Adaptation at the level of the gene is givingway to adaptation at the level of the organism and higher-order assemblages of organisms. These ideas impact on the theories of how cooperation might have evolved. Two of the theories, i.e. that cooperating individuals are genetically related or that they cooperate for self-interested reasons, have been accepted for a long time. The idea that adaptation takes place at the level of groups is much more controversial. However, bringing together studies of development with those of evolution is taking away much of the heat in the debate about the evolution of group behaviour.

  6. [Schizophrenia, environment and epigenetics].

    Science.gov (United States)

    Must, Anita; Janka, Zoltan; Horvath, Szatmar

    2011-12-01

    Psychotic, cognitive and affective symptoms defining schizophrenia may, though much less severe, manifest themselves in up to 10 to 20% of the general population. What explains the fact that in certain cases the symptoms require even constant medical supervision, while others are capable of living a normal life within social conventions? Which factors lead to the transition of mild, subclinical manifestations and vulnerability indicators towards the outburst of one of the most severe and depriving mental disorders? Genetic susceptibility is undoubtedly crucial. More recent research findings emphasize the modifying effect of specific environmental factors on gene expression. The gene-environment interplay may induce so-called epigenetic alterations which may manifest themselves over several generations. Future integrative, multi-dimensional and flexible schizophrenia research approaches focusing on the identification of neurobiological and cognitive outcomes are much needed to understand disease vulnerability, susceptibility mechanisms, periods and interactions. Research methods may differ, but our aim is common - establishing more effective diagnostic and therapeutic interventions.

  7. Environment, epigenetics and reproduction.

    Science.gov (United States)

    Skinner, Michael K

    2017-07-01

    A conference summary of the third biannual Kenya Africa Conference "Environment, Epigenetics and Reproduction" is provided. A partial special Environmental Epigenetics issue containing a number of papers in Volume 3, Issue 3 and 4 are discussed.

  8. Epigenetics and Epigenomics of Plants.

    Science.gov (United States)

    Yadav, Chandra Bhan; Pandey, Garima; Muthamilarasan, Mehanathan; Prasad, Manoj

    2018-01-23

    The genetic material DNA in association with histone proteins forms the complex structure called chromatin, which is prone to undergo modification through certain epigenetic mechanisms including cytosine DNA methylation, histone modifications, and small RNA-mediated methylation. Alterations in chromatin structure lead to inaccessibility of genomic DNA to various regulatory proteins such as transcription factors, which eventually modulates gene expression. Advancements in high-throughput sequencing technologies have provided the opportunity to study the epigenetic mechanisms at genome-wide levels. Epigenomic studies using high-throughput technologies will widen the understanding of mechanisms as well as functions of regulatory pathways in plant genomes, which will further help in manipulating these pathways using genetic and biochemical approaches. This technology could be a potential research tool for displaying the systematic associations of genetic and epigenetic variations, especially in terms of cytosine methylation onto the genomic region in a specific cell or tissue. A comprehensive study of plant populations to correlate genotype to epigenotype and to phenotype, and also the study of methyl quantitative trait loci (QTL) or epiGWAS, is possible by using high-throughput sequencing methods, which will further accelerate molecular breeding programs for crop improvement. Graphical Abstract.

  9. Ethical and clinical practice considerations for genetic counselors related to direct-to-consumer marketing of genetic tests.

    Science.gov (United States)

    Wade, Christopher H; Wilfond, Benjamin S

    2006-11-15

    Several companies utilize direct-to-consumer (DTC) advertising for genetic tests and some, but not all, bypass clinician involvement by offering DTC purchase of the tests. This article examines how DTC marketing strategies may affect genetic counselors, using available cardiovascular disease susceptibility tests as an illustration. The interpretation of these tests is complex and includes consideration of clinical validity and utility, and the further complications of gene-environment interactions and pleiotropy. Although it is unclear to what extent genetic counselors will encounter clients who have been exposed to DTC marketing strategies, these strategies may influence genetic counseling interactions if they produce directed interest in specific tests and unrealistic expectations for the tests' capacity to predict disease. Often, a client's concern about risk for cardiovascular diseases is best addressed by established clinical tests and a family history assessment. Ethical dilemmas may arise for genetic counselors who consider whether to accept clients who request test interpretation or to order DTC-advertised tests that require a clinician's authorization. Genetic counselors' obligations to care for clients extend to interpreting DTC tests, although this obligation may be fulfilled by referral or consultation with specialists. Genetic counselors do not have an obligation to order DTC-advertised tests that have minimal clinical validity and utility at a client's request. This can be a justified restriction on autonomy based on consideration of risks to the client, the costs, and the implications for society. Published 2006 Wiley-Liss, Inc.

  10. Direct-to-consumer sales of genetic services on the Internet.

    Science.gov (United States)

    Gollust, Sarah E; Wilfond, Benjamin S; Hull, Sara Chandros

    2003-01-01

    PURPOSE The increasing use of the Internet to obtain genetics information and to order medical services without a prescription, combined with a rise in direct-to-consumer marketing for genetic testing, suggests the potential for the Internet to be used to sell genetic services. METHODS A systematic World Wide Web search was conducted in May 2002 to assess the availability of genetic services sold directly to consumers on the Internet. RESULTS Out of 105 sites that offered genetic services directly, most offered non-health-related services, including parentage confirmation testing (83%), identity testing (56%), and DNA banking (24%); however, health-related genetic tests were offered through 14 sites (13%). The health-related genetic tests available ranged from standard tests, such as hemochromatosis and cystic fibrosis, to more unconventional tests related to nutrition, behavior, and aging. Of these 14 sites, 5 described risks associated with the genetic services and 6 described the availability of counseling. CONCLUSIONS The availability of direct sales of health-related genetic tests creates the potential for inadequate pretest decision making, misunderstanding test results, and access to tests of questionable clinical value.

  11. Lamarck rises from his grave: parental environment-induced epigenetic inheritance in model organisms and humans.

    Science.gov (United States)

    Wang, Yan; Liu, Huijie; Sun, Zhongsheng

    2017-11-01

    Organisms can change their physiological/behavioural traits to adapt and survive in changed environments. However, whether these acquired traits can be inherited across generations through non-genetic alterations has been a topic of debate for over a century. Emerging evidence indicates that both ancestral and parental experiences, including nutrition, environmental toxins, nurturing behaviour, and social stress, can have powerful effects on the physiological, metabolic and cellular functions in an organism. In certain circumstances, these effects can be transmitted across several generations through epigenetic (i.e. non-DNA sequence-based rather than mutational) modifications. In this review, we summarize recent evidence on epigenetic inheritance from parental environment-induced developmental and physiological alterations in nematodes, fruit flies, zebrafish, rodents, and humans. The epigenetic modifications demonstrated to be both susceptible to modulation by environmental cues and heritable, including DNA methylation, histone modification, and small non-coding RNAs, are also summarized. We particularly focus on evidence that parental environment-induced epigenetic alterations are transmitted through both the maternal and paternal germlines and exert sex-specific effects. The thought-provoking data presented here raise fundamental questions about the mechanisms responsible for these phenomena. In particular, the means that define the specificity of the response to parental experience in the gamete epigenome and that direct the establishment of the specific epigenetic change in the developing embryos, as well as in specific tissues in the descendants, remain obscure and require elucidation. More precise epigenetic assessment at both the genome-wide level and single-cell resolution as well as strategies for breeding at relatively sensitive periods of development and manipulation aimed at specific epigenetic modification are imperative for identifying parental

  12. Individuality and epigenetics in obesity.

    Science.gov (United States)

    Campión, J; Milagro, F I; Martínez, J A

    2009-07-01

    Excessive weight gain arises from the interactions among environmental factors, genetic predisposition and the individual behavior. However, it is becoming evident that interindividual differences in obesity susceptibility depend also on epigenetic factors. Epigenetics studies the heritable changes in gene expression that do not involve changes to the underlying DNA sequence. These processes include DNA methylation, covalent histone modifications, chromatin folding and, more recently described, the regulatory action of miRNAs and polycomb group complexes. In this review, we focus on experimental evidences concerning dietary factors influencing obesity development by epigenetic mechanisms, reporting treatment doses and durations. Moreover, we present a bioinformatic analysis of promoter regions for the search of future epigenetic biomarkers of obesity, including methylation pattern analyses of several obesity-related genes (epiobesigenes), such as FGF2, PTEN, CDKN1A and ESR1, implicated in adipogenesis, SOCS1/SOCS3, in inflammation, and COX7A1 LPL, CAV1, and IGFBP3, in intermediate metabolism and insulin signalling. The identification of those individuals that at an early age could present changes in the methylation profiles of specific genes could help to predict their susceptibility to later develop obesity, which may allow to prevent and follow-up its progress, as well as to research and develop newer therapeutic approaches.

  13. Epigenetic mechanism of radiation carcinogenesis

    International Nuclear Information System (INIS)

    Niwa, Ohtsura

    1995-01-01

    Carcinogenic action of radiations has long been thought to be due to its mutagenic activity. Since DNA damage is induced and distributes in a stochastic fashion, radiation induction of cancers was also assumed to follow a stochastic kinetics. However, recent progress in radiation research has revealed that some features of radiation carcinogenesis are not explainable by the simple action of radiation as a DNA damaging and mutagenic agent. Firstly, frequencies of radiation-induced transformation in vitro and radiation-induced mammary cancers in rats are too high to be accounted for by the frequency of radiation-induced mutation. Secondly, trans-generation carcinogenesis among F1 mice born to irradiated parents occurs also much more frequently than to be predicted by the frequency of radiation induced germline mutation. Thirdly, multistage carcinogenesis theory predicts that carcinogens give hits to the target cells so as to shorten the latency of cancers. However, latencies of radiation induced solid cancers among atomic bomb survivors are similar to those of the control population. Fourthly, although radiation elevates the frequency of cancers, the induced cancers seem to share the same spectrum of cancer types as in the unirradiated control populations. This suggests that radiation induces cancer by enhancement of the spontaneous carcinogenesis process. These data suggest that the first step of radiation carcinogenesis may not be the direct induction of mutation. Radiation may induce genetic instability which increases the spontaneous mutation rate in the cells to produce carcinogenic mutations. Growth stimulatory effect of radiation may also contribute to the process. Thus, epigenetic, but not genetic effect of radiation might better contribute in the process of carcinogenesis. (author)

  14. Epigenetic Mechanisms and Therapeutic Perspectives for Neurodevelopmental Disorders

    Directory of Open Access Journals (Sweden)

    Kunio Miyake

    2012-04-01

    Full Text Available The number of children with mild neurodevelopmental disorders, such as autism, has been recently increasing in advanced countries. This increase is probably caused by environmental factors rather than genetic factors, because it is unlikely that genetic mutation rates suddenly increased within a short period. Epigenetics is a mechanism that regulates gene expression, depending not on the underlying DNA sequence but on the chemical modifications of DNA and histone proteins. Because mental stress can alter the epigenetic status in neuronal cells, environmental factors may alter brain function through epigenetic changes. However, one advantage of epigenetic changes is their reversibility. Therefore, diseases due to abnormal epigenetic regulation are theoretically treatable. In fact, several drugs for treating mental diseases are known to have restoring effects on aberrant epigenetic statuses, and a novel therapeutic strategy targeting gene has been developed. In this review, we discuss epigenetic mechanisms of congenital and acquired neurodevelopmental disorders, drugs with epigenetic effects, novel therapeutic strategies for epigenetic diseases, and future perspectives in epigenetic medicine.

  15. Epigenetic changes in solid and hematopoietic tumors.

    Science.gov (United States)

    Toyota, Minoru; Issa, Jean-Pierre J

    2005-10-01

    There are three connected molecular mechanisms of epigenetic cellular memory in mammalian cells: DNA methylation, histone modifications, and RNA interference. The first two have now been firmly linked to neoplastic transformation. Hypermethylation of CpG-rich promoters triggers local histone code modifications resulting in a cellular camouflage mechanism that sequesters gene promoters away from transcription factors and results in stable silencing. This normally restricted mechanism is ubiquitously used in cancer to silence hundreds of genes, among which some critically contribute to the neoplastic phenotype. Virtually every pathway important to cancer formation is affected by this process. Methylation profiling of human cancers reveals tissue-specific epigenetic signatures, as well as tumor-specific signatures, reflecting in particular the presence of epigenetic instability in a subset of cancers affected by the CpG island methylator phenotype. Generally, methylation patterns can be traced to a tissue-specific, proliferation-dependent accumulation of aberrant promoter methylation in aging tissues, a process that can be accelerated by chronic inflammation and less well-defined mechanisms including, possibly, diet and genetic predisposition. The epigenetic machinery can also be altered in cancer by specific lesions in epigenetic effector genes, or by aberrant recruitment of these genes by mutant transcription factors and coactivators. Epigenetic patterns are proving clinically useful in human oncology via risk assessment, early detection, and prognostic classification. Pharmacologic manipulation of these patterns-epigenetic therapy-is also poised to change the way we treat cancer in the clinic.

  16. Epigenetics: ambiguities and implications.

    Science.gov (United States)

    Stotz, Karola; Griffiths, Paul

    2016-12-01

    Everyone has heard of 'epigenetics', but the term means different things to different researchers. Four important contemporary meanings are outlined in this paper. Epigenetics in its various senses has implications for development, heredity, and evolution, and also for medicine. Concerning development, it cements the vision of a reactive genome strongly coupled to its environment. Concerning heredity, both narrowly epigenetic and broader 'exogenetic' systems of inheritance play important roles in the construction of phenotypes. A thoroughly epigenetic model of development and evolution was Waddington's aim when he introduced the term 'epigenetics' in the 1940s, but it has taken the modern development of molecular epigenetics to realize this aim. In the final sections of the paper we briefly outline some further implications of epigenetics for medicine and for the nature/nurture debate.

  17. Genetic trends of selection for pelt traits in Karakul sheep I. Direct ...

    African Journals Online (AJOL)

    Genetic trends of selection for pelt traits in Karakul sheep. I. Direct ... development in the Karakul Wereestimated with the Animal Model in four selection lines and in a control flock over ..... Selection experiments in laboratory and domestic.

  18. Epigenetic Aspects of Posttraumatic Stress Disorder

    Directory of Open Access Journals (Sweden)

    Ulrike Schmidt

    2011-01-01

    Full Text Available Development of psychiatric diseases such as posttraumatic stress disorder (PTSD invokes, as with most complex diseases, both genetic and environmental factors. The era of genome-wide high throughput technologies has sparked the initiation of genotype screenings in large cohorts of diseased and control individuals, but had limited success in identification of disease causing genetic variants. It has become evident that these efforts at the genomic level need to be complemented with endeavours in elucidating the proteome, transcriptome and epigenetic profiles. Epigenetics is attractive in particular because there is accumulating evidence that the lasting impact of adverse life events is reflected in certain covalent modifications of the chromatin.

  19. Environmental chemical exposures and human epigenetics

    Science.gov (United States)

    Hou, Lifang; Zhang, Xiao; Wang, Dong; Baccarelli, Andrea

    2012-01-01

    Every year more than 13 million deaths worldwide are due to environmental pollutants, and approximately 24% of diseases are caused by environmental exposures that might be averted through preventive measures. Rapidly growing evidence has linked environmental pollutants with epigenetic variations, including changes in DNA methylation, histone modifications and microRNAs. Environ mental chemicals and epigenetic changes All of these mechanisms are likely to play important roles in disease aetiology, and their modifications due to environmental pollutants might provide further understanding of disease aetiology, as well as biomarkers reflecting exposures to environmental pollutants and/or predicting the risk of future disease. We summarize the findings on epigenetic alterations related to environmental chemical exposures, and propose mechanisms of action by means of which the exposures may cause such epigenetic changes. We discuss opportunities, challenges and future directions for future epidemiology research in environmental epigenomics. Future investigations are needed to solve methodological and practical challenges, including uncertainties about stability over time of epigenomic changes induced by the environment, tissue specificity of epigenetic alterations, validation of laboratory methods, and adaptation of bioinformatic and biostatistical methods to high-throughput epigenomics. In addition, there are numerous reports of epigenetic modifications arising following exposure to environmental toxicants, but most have not been directly linked to disease endpoints. To complete our discussion, we also briefly summarize the diseases that have been linked to environmental chemicals-related epigenetic changes. PMID:22253299

  20. Direct-to-Consumer Genetic Testing: Helping Patients Make Informed Choices
.

    Science.gov (United States)

    Mahon, Suzanne M

    2018-02-01

    Using direct-to-consumer genetic testing (DTCGT), individuals can order a genetic test, collect and submit a saliva sample, and obtain results about their genetic risk for a variety of traits and health conditions without involving a healthcare provider. Potential benefits of DTCGT include personal control over genetic information and health management decisions, whereas potential risks include misinterpretation of results, psychosocial distress, and lack of informed consent. Oncology nurses can provide education, support, and advocacy to enable patients to truly understand the positives and negatives associated with DTCGT.
.

  1. Direct-to-consumer genetic testing: perceptions, problems, and policy responses.

    Science.gov (United States)

    Caulfield, Timothy; McGuire, Amy L

    2012-01-01

    Direct-to-consumer (DTC) genetic testing has attracted a great amount of attention from policy makers, the scientific community, professional groups, and the media. Although it is unclear what the public demand is for these services, there does appear to be public interest in personal genetic risk information. As a result, many commentators have raised a variety of social, ethical, and regulatory issues associated with this emerging industry, including privacy issues, ensuring that DTC companies provide accurate information about the risks and limitations of their services, the possible adverse impact of DTC genetic testing on healthcare systems, and concern about how individuals may interpret and react to genetic risk information.

  2. Epigenetic regulation of female puberty.

    Science.gov (United States)

    Lomniczi, Alejandro; Wright, Hollis; Ojeda, Sergio R

    2015-01-01

    Substantial progress has been made in recent years toward deciphering the molecular and genetic underpinnings of the pubertal process. The availability of powerful new methods to interrogate the human genome has led to the identification of genes that are essential for puberty to occur. Evidence has also emerged suggesting that the initiation of puberty requires the coordinated activity of gene sets organized into functional networks. At a cellular level, it is currently thought that loss of transsynaptic inhibition, accompanied by an increase in excitatory inputs, results in the pubertal activation of GnRH release. This concept notwithstanding, a mechanism of epigenetic repression targeting genes required for the pubertal activation of GnRH neurons was recently identified as a core component of the molecular machinery underlying the central restraint of puberty. In this chapter we will discuss the potential contribution of various mechanisms of epigenetic regulation to the hypothalamic control of female puberty. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Transcriptomic and genetic analysis of direct interspecies electron transfer

    DEFF Research Database (Denmark)

    Shrestha, Pravin Malla; Rotaru, Amelia-Elena; Summers, Zarath M

    2013-01-01

    The possibility that metatranscriptomic analysis could distinguish between direct interspecies electron transfer (DIET) and H2 interspecies transfer (HIT) in anaerobic communities was investigated by comparing gene transcript abundance in cocultures in which Geobacter sulfurreducens....... These results demonstrate that there are unique gene expression patterns that distinguish DIET from HIT and suggest that metatranscriptomics may be a promising route to investigate interspecies electron transfer pathways in more-complex environments....

  4. Environmental Epigenetics: Crossroad between Public Health, Lifestyle, and Cancer Prevention

    Science.gov (United States)

    Romani, Massimo; Pistillo, Maria Pia; Banelli, Barbara

    2015-01-01

    Epigenetics provides the key to transform the genetic information into phenotype and because of its reversibility it is considered an ideal target for therapeutic interventions. This paper reviews the basic mechanisms of epigenetic control: DNA methylation, histone modifications, chromatin remodeling, and ncRNA expression and their role in disease development. We describe also the influence of the environment, lifestyle, nutritional habits, and the psychological influence on epigenetic marks and how these factors are related to cancer and other diseases development. Finally we discuss the potential use of natural epigenetic modifiers in the chemoprevention of cancer to link together public health, environment, and lifestyle. PMID:26339624

  5. Epigenetic Regulation in Particulate Matter-Mediated Cardiopulmonary Toxicities: A Systems Biology Perspective.

    Science.gov (United States)

    Wang, Ting; Garcia, Joe Gn; Zhang, Wei

    2012-12-01

    Particulate matter (PM) air pollution exerts significant adverse health effects in global populations, particularly in developing countries with extensive air pollution. Understanding of the mechanisms of PM-induced health effects including the risk for cardiovascular diseases remains limited. In addition to the direct cellular physiological responses such as mitochondrial dysfunction and oxidative stress, PM mediates remarkable dysregulation of gene expression, especially in cardiovascular tissues. The PM-mediated gene dysregulation is likely to be a complex mechanism affected by various genetic and non-genetic factors. Notably, PM is known to alter epigenetic markers (e.g., DNA methylation and histone modifications), which may contribute to air pollution-mediated health consequences including the risk for cardiovascular diseases. Notably, epigenetic changes induced by ambient PM exposure have emerged to play a critical role in gene regulation. Though the underlying mechanism(s) are not completely clear, the available evidence suggests that the modulated activities of DNA methyltransferase (DNMT), histone acetylase (HAT) and histone deacetylase (HDAC) may contribute to the epigenetic changes induced by PM or PM-related chemicals. By employing genome-wide epigenomic and systems biology approaches, PM toxicogenomics could conceivably progress greatly with the potential identification of individual epigenetic loci associated with dysregulated gene expression after PM exposure, as well the interactions between epigenetic pathways and PM. Furthermore, novel therapeutic targets based on epigenetic markers could be identified through future epigenomic studies on PM-mediated cardiopulmonary toxicities. These considerations collectively inform the future population health applications of genomics in developing countries while benefiting global personalized medicine at the same time.

  6. Epigenetics and Cellular Metabolism

    Directory of Open Access Journals (Sweden)

    Wenyi Xu

    2016-01-01

    Full Text Available Living eukaryotic systems evolve delicate cellular mechanisms for responding to various environmental signals. Among them, epigenetic machinery (DNA methylation, histone modifications, microRNAs, etc. is the hub in transducing external stimuli into transcriptional response. Emerging evidence reveals the concept that epigenetic signatures are essential for the proper maintenance of cellular metabolism. On the other hand, the metabolite, a main environmental input, can also influence the processing of epigenetic memory. Here, we summarize the recent research progress in the epigenetic regulation of cellular metabolism and discuss how the dysfunction of epigenetic machineries influences the development of metabolic disorders such as diabetes and obesity; then, we focus on discussing the notion that manipulating metabolites, the fuel of cell metabolism, can function as a strategy for interfering epigenetic machinery and its related disease progression as well.

  7. The Emerging Role of Epigenetics in Inflammation and Immunometabolism.

    Science.gov (United States)

    Raghuraman, Sukanya; Donkin, Ida; Versteyhe, Soetkin; Barrès, Romain; Simar, David

    2016-11-01

    Recent research developments have shed light on the risk factors contributing to metabolic complications, implicating both genetic and environmental factors, potentially integrated by epigenetic mechanisms. Distinct epigenetic changes in immune cells are frequently observed in obesity and type 2 diabetes mellitus, and these are associated with alterations in the phenotype, function, and trafficking patterns of these cells. The first step in the development of effective therapeutic strategies is the identification of distinct epigenetic signatures associated with metabolic disorders. In this review we provide an overview of the epigenetic mechanisms influencing immune cell phenotype and function, summarize current knowledge about epigenetic changes affecting immune functions in the context of metabolic diseases, and discuss the therapeutic options currently available to counteract epigenetically driven metabolic complications. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Epigenetics and obesity

    OpenAIRE

    Stöger, Reinhard

    2008-01-01

    Common DNA sequence variants inadequately explain variability in fat mass among individuals. Abnormal body weights are characteristic of specific imprinted-gene disorders. However, the relevance of imprinted genes to our understanding of obesity among the general population is uncertain. Hitherto unidentified imprinted genes and epigenetic mosaicism are two of the challenges for this emerging field of epigenetics. Subtle epigenetic differences in imprinted genes and gene networks are likely t...

  9. The impact of direct-to-consumer marketing of cancer genetic testing on women according to their genetic risk.

    Science.gov (United States)

    Lowery, Jan T; Byers, Tim; Axell, Lisen; Ku, Lisa; Jacobellis, Jillian

    2008-12-01

    To assess the impact of direct-to-consumer marketing for genetic testing among women of varying genetic risk for breast and ovarian cancer. Telephone surveys were conducted with 315 women in Denver, Colorado, one target audience for the Myriad BRACAnalysis ad campaign. Genetic risk was determined from personal and family history and grouped by probability of having a BRCA1/2 mutation (low or =10%). High-risk women were more knowledgeable about BRACAnalysis and more likely to recall the media ads than were low-risk women (60 vs. 39%, P audience. Concern about breast cancer was not appreciably increased. A large percentage of low-risk women (not candidates for testing) expressed interest in testing, suggesting the campaign was too broad. A campaign targeted at high-risk women, who may benefit from testing might be preferred.

  10. Risk assesment in the context of EC directives on genetically modified organisms

    Energy Technology Data Exchange (ETDEWEB)

    Meer, P.J. van der [Ministry for the Environment (Netherlands)

    1992-07-01

    The introduction of these new molecular technologies initiated an international discussion on the safety in biotechnology. In 1974 one of the pioneers of this new technology, Paul Berg, expressed his view on the potential risks of recombinant DNA applications in the famous 'Berg letter', leading to a self-imposed moratorium on certain experiments. Following the Berg letter and the Asilomar convention, much international attention has been given to the question of safety in biotechnology. This attention resulted in hundreds of documents, research programmes, guidelines and regulations. This resulted, among others, in two EC Directives on genetically modified organisms: the EC Directive 90/219/EEC on the contained use of genetically modified micro-organisms, and Directive 90/220/EEC on the release of genetically modified organisms. These directives lay down a system for harmonization of risk assessment and risk management with regard to the safety for human health and the environment.

  11. Risk assesment in the context of EC directives on genetically modified organisms

    International Nuclear Information System (INIS)

    Meer, P.J. van der

    1992-01-01

    The introduction of these new molecular technologies initiated an international discussion on the safety in biotechnology. In 1974 one of the pioneers of this new technology, Paul Berg, expressed his view on the potential risks of recombinant DNA applications in the famous 'Berg letter', leading to a self-imposed moratorium on certain experiments. Following the Berg letter and the Asilomar convention, much international attention has been given to the question of safety in biotechnology. This attention resulted in hundreds of documents, research programmes, guidelines and regulations. This resulted, among others, in two EC Directives on genetically modified organisms: the EC Directive 90/219/EEC on the contained use of genetically modified micro-organisms, and Directive 90/220/EEC on the release of genetically modified organisms. These directives lay down a system for harmonization of risk assessment and risk management with regard to the safety for human health and the environment

  12. Direct to consumer genetic testing-law and policy concerns in Ireland.

    Science.gov (United States)

    de Paor, Aisling

    2017-11-25

    With rapid scientific and technological advances, the past few years has witnessed the emergence of a new genetic era and a growing understanding of the genetic make-up of human beings. These advances have propelled the introduction of companies offering direct to consumer (DTC) genetic testing, which facilitates the direct provision of such tests to consumers, (for example, via the internet). Although DTC genetic testing offers benefits by enhancing consumer accessibility to such technology, promoting proactive healthcare and increasing genetic awareness, it presents a myriad of challenges, from an ethical, legal and regulatory perspective. As DTC genetic testing usually eliminates the need for a medical professional in accessing genetic tests, this lack of professional guidance and counselling may result in misinterpretation and confusion regarding results. In addition, an evident concern relates to the scientific validity and quality of these tests. A further problem arising is the lack or inadequacy of regulation in this field. Despite the increasing accessibility of DTC genetic testing, this legislative vacuum is apparent in Ireland, where there is no concrete legislation. This article explores the main ethical, legal and regulatory issues arising with the advent of rapid advances in DTC genetic testing in Ireland. Further, with inevitable future advances in genetic science, as well as increasing internet accessibility, the challenges presented are likely to become more amplified. In consideration of the ethical and legal challenges, this paper highlights the regulation of DTC genetic testing as a growing concern in Ireland, recognising its importance to both the scientific community as well as in respect of enhancing consumer confidence in such technologies.

  13. Dominance genetic variance for traits under directional selection in Drosophila serrata.

    Science.gov (United States)

    Sztepanacz, Jacqueline L; Blows, Mark W

    2015-05-01

    In contrast to our growing understanding of patterns of additive genetic variance in single- and multi-trait combinations, the relative contribution of nonadditive genetic variance, particularly dominance variance, to multivariate phenotypes is largely unknown. While mechanisms for the evolution of dominance genetic variance have been, and to some degree remain, subject to debate, the pervasiveness of dominance is widely recognized and may play a key role in several evolutionary processes. Theoretical and empirical evidence suggests that the contribution of dominance variance to phenotypic variance may increase with the correlation between a trait and fitness; however, direct tests of this hypothesis are few. Using a multigenerational breeding design in an unmanipulated population of Drosophila serrata, we estimated additive and dominance genetic covariance matrices for multivariate wing-shape phenotypes, together with a comprehensive measure of fitness, to determine whether there is an association between directional selection and dominance variance. Fitness, a trait unequivocally under directional selection, had no detectable additive genetic variance, but significant dominance genetic variance contributing 32% of the phenotypic variance. For single and multivariate morphological traits, however, no relationship was observed between trait-fitness correlations and dominance variance. A similar proportion of additive and dominance variance was found to contribute to phenotypic variance for single traits, and double the amount of additive compared to dominance variance was found for the multivariate trait combination under directional selection. These data suggest that for many fitness components a positive association between directional selection and dominance genetic variance may not be expected. Copyright © 2015 by the Genetics Society of America.

  14. Epigenetic Regulation of Adipokines

    Directory of Open Access Journals (Sweden)

    Tho X. Pham

    2017-08-01

    Full Text Available Adipose tissue expansion in obesity leads to changes in the expression of adipokines, adipocyte-specific hormones that can regulate whole body energy metabolism. Epigenetic regulation of gene expression is a mechanism by which cells can alter gene expression through the modifications of DNA and histones. Epigenetic mechanisms, such as DNA methylation and histone modifications, are intimately tied to energy metabolism due to their dependence on metabolic intermediates such as S-adenosylmethionine and acetyl-CoA. Altered expression of adipokines in obesity may be due to epigenetic changes. The goal of this review is to highlight current knowledge of epigenetic regulation of adipokines.

  15. Direct-to-consumer genetic testing in Slovenia: availability, ethical dilemmas and legislation.

    Science.gov (United States)

    Vrecar, Irena; Peterlin, Borut; Teran, Natasa; Lovrecic, Luca

    2015-01-01

    Over the last few years, many private companies are advertising direct-to-consumer genetic testing (DTC GT), mostly with no or only minor clinical utility and validity of tests and without genetic counselling. International professional community does not approve provision of DTC GT and situation in some EU countries has been analysed already. The aim of our study was to analyse current situation in the field of DTC GT in Slovenia and related legal and ethical issues. Information was retrieved through internet search, performed independently by two authors, structured according to individual private company and the types of offered genetic testing. Five private companies and three Health Insurance Companies offer DTC GT and it is provided without genetic counselling. Available tests include testing for breast cancer, tests with other health-related information (complex diseases, drug responses) and other tests (nutrigenetic, ancestry, paternity). National legislation is currently being developed and Council of Experts in Medical Genetics has issued an opinion about Genetic Testing and Commercialization of Genetic Tests in Slovenia. Despite the fact that Slovenia has signed the Additional protocol to the convention on human rights and biomedicine, concerning genetic testing for health purposes, DTC GT in Slovenia is present and against all international recommendations. There is lack of or no medical supervision, clinical validity and utility of tests and inappropriate genetic testing of minors is available. There is urgent need for regulation of ethical, legal, and social aspects. National legislation on DTC GT is being prepared.

  16. Potential of epigenetic therapies in the management of solid tumors

    International Nuclear Information System (INIS)

    Valdespino, Victor; Valdespino, Patricia M

    2015-01-01

    Cancer is a complex disease with both genetic and epigenetic origins. The growing field of epigenetics has contributed to our understanding of oncogenesis and tumor progression, and has allowed the development of novel therapeutic drugs. First-generation epigenetic inhibitor drugs have obtained modest clinical results in two types of hematological malignancy. Second-generation epigenetic inhibitors are in development, and have intrinsically greater selectivity for their molecular targets. Solid tumors are more genetic and epigenetically complex than hematological malignancies, but the transcriptome and epigenome biomarkers have been identified for many of these malignancies. This solid tumor molecular aberration profile may be modified using specific or quasi-specific epidrugs together with conventional and innovative anticancer treatments. In this critical review, we briefly analyze the strategies to select the targeted epigenetic changes, enumerate the second-generation epigenetic inhibitors, and describe the main signs indicating the potential of epigenetic therapies in the management of solid tumors. We also highlight the work of consortia or academic organizations that support the undertaking of human epigenetic therapeutic projects as well as some examples of transcriptome/epigenome profile determination in clinical assessment of cancer patients treated with epidrugs. There is a good chance that epigenetic therapies will be able to be used in patients with solid tumors in the future. This may happen soon through collaboration of diverse scientific groups, making the selection of targeted epigenetic aberration(s) more rapid, the design and probe of drug candidates, accelerating in vitro and in vivo assays, and undertaking new cancer epigenetic-therapy clinical trails

  17. Characterization of three different clusters of 18S-26S ribosomal DNA genes in the sea urchin P. lividus: Genetic and epigenetic regulation synchronous to 5S rDNA.

    Science.gov (United States)

    Bellavia, Daniele; Dimarco, Eufrosina; Caradonna, Fabio

    2016-04-15

    We previously reported the characterization 5S ribosomal DNA (rDNA) clusters in the common sea urchin Paracentrotus lividus and demonstrated the presence of DNA methylation-dependent silencing of embryo specific 5S rDNA cluster in adult tissue. In this work, we show genetic and epigenetic characterization of 18S-26S rDNA clusters in this specie. The results indicate the presence of three different 18S-26S rDNA clusters with different Non-Transcribed Spacer (NTS) regions that have different chromosomal localizations. Moreover, we show that the two largest clusters are hyper-methylated in the promoter-containing NTS regions in adult tissues, as in the 5S rDNA. These findings demonstrate an analogous epigenetic regulation in small and large rDNA clusters and support the logical synchronism in building ribosomes. In fact, all the ribosomal RNA genes must be synchronously and equally transcribed to perform their unique final product. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Advances in epigenetics and epigenomics for neurodegenerative diseases.

    Science.gov (United States)

    Qureshi, Irfan A; Mehler, Mark F

    2011-10-01

    In the post-genomic era, epigenetic factors-literally those that are "over" or "above" genetic ones and responsible for controlling the expression and function of genes-have emerged as important mediators of development and aging; gene-gene and gene-environmental interactions; and the pathophysiology of complex disease states. Here, we provide a brief overview of the major epigenetic mechanisms (ie, DNA methylation, histone modifications and chromatin remodeling, and non-coding RNA regulation). We highlight the nearly ubiquitous profiles of epigenetic dysregulation that have been found in Alzheimer's and other neurodegenerative diseases. We also review innovative methods and technologies that enable the characterization of individual epigenetic modifications and more widespread epigenomic states at high resolution. We conclude that, together with complementary genetic, genomic, and related approaches, interrogating epigenetic and epigenomic profiles in neurodegenerative diseases represent important and increasingly practical strategies for advancing our understanding of and the diagnosis and treatment of these disorders.

  19. Computational Modelling Approaches on Epigenetic Factors in Neurodegenerative and Autoimmune Diseases and Their Mechanistic Analysis

    Directory of Open Access Journals (Sweden)

    Afroza Khanam Irin

    2015-01-01

    Full Text Available Neurodegenerative as well as autoimmune diseases have unclear aetiologies, but an increasing number of evidences report for a combination of genetic and epigenetic alterations that predispose for the development of disease. This review examines the major milestones in epigenetics research in the context of diseases and various computational approaches developed in the last decades to unravel new epigenetic modifications. However, there are limited studies that systematically link genetic and epigenetic alterations of DNA to the aetiology of diseases. In this work, we demonstrate how disease-related epigenetic knowledge can be systematically captured and integrated with heterogeneous information into a functional context using Biological Expression Language (BEL. This novel methodology, based on BEL, enables us to integrate epigenetic modifications such as DNA methylation or acetylation of histones into a specific disease network. As an example, we depict the integration of epigenetic and genetic factors in a functional context specific to Parkinson’s disease (PD and Multiple Sclerosis (MS.

  20. The placental gateway of maternal transgenerational epigenetic ...

    Indian Academy of Sciences (India)

    While much of our understanding of genetic inheritance is based on the genome of the organism, it is becoming clear that there is an ample amount of epigenetic inheritance, which though reversible, escapes erasing process during gametogenesis and goes on to the next generation. Several examples of transgenerational ...

  1. Nonlinear Epigenetic Variance: Review and Simulations

    Science.gov (United States)

    Kan, Kees-Jan; Ploeger, Annemie; Raijmakers, Maartje E. J.; Dolan, Conor V.; van Der Maas, Han L. J.

    2010-01-01

    We present a review of empirical evidence that suggests that a substantial portion of phenotypic variance is due to nonlinear (epigenetic) processes during ontogenesis. The role of such processes as a source of phenotypic variance in human behaviour genetic studies is not fully appreciated. In addition to our review, we present simulation studies…

  2. Epigenetics and Bruxism: Possible Role of Epigenetics in the Etiology of Bruxism.

    Science.gov (United States)

    Čalić, Aleksandra; Peterlin, Borut

    2015-01-01

    Bruxism is defined as a repetitive jaw muscle activity characterized by clenching or grinding of the teeth and/or bracing or thrusting of the mandible. There are two distinct circadian phenotypes for bruxism: sleep bruxism (SB) and awake bruxism, which are considered separate entities due to the putative difference in their etiology and phenotypic variance. The detailed etiology of bruxism so far remains unknown. Recent theories suggest the central regulation of certain pathophysiological or psychological pathways. Current proposed causes of bruxism appear to be a combination of genetic and environmental (G×E) factors, with epigenetics providing a robust framework for investigating G×E interactions, and their involvement in bruxism makes it a suitable candidate for epigenetic research. Both types of bruxism are associated with certain epigenetically determined disorders, such as Rett syndrome (RTT), Prader-Willi syndrome (PWS), and Angelman syndrome (AS), and these associations suggest a mechanistic link between epigenetic deregulation and bruxism. The present article reviews the possible role of epigenetic mechanisms in the etiology of both types of bruxism based on the epigenetic pathways involved in the pathophysiology of RTT, PWS, and AS, and on other epigenetic disruptions associated with risk factors for bruxism, including sleep disorders, altered stress response, and psychopathology.

  3. [Direct genetic manipulation and criminal code in Venezuela: absolute criminal law void?].

    Science.gov (United States)

    Cermeño Zambrano, Fernando G De J

    2002-01-01

    The judicial regulation of genetic biotechnology applied to the human genome is of big relevance currently in Venezuela due to the drafting of an innovative bioethical law in the country's parliament. This article will highlight the constitutional normative of Venezuela's 1999 Constitution regarding this subject, as it establishes the framework from which this matter will be legally regulated. The approach this article makes towards the genetic biotechnology applied to the human genome is made taking into account the Venezuelan penal law and by highlighting the violent genetic manipulations that have criminal relevance. The genetic biotechnology applied to the human genome has another important relevance as a consequence of the reformulation of the Venezuelan Penal Code discussed by the country's National Assembly. Therefore, a concise study of the country's penal code will be made in this article to better understand what judicial-penal properties have been protected by the Venezuelan penal legislation. This last step will enable us to identify the penal tools Venezuela counts on to face direct genetic manipulations. We will equally indicate the existing punitive loophole and that should be covered by the penal legislator. In conclusion, this essay concerns criminal policy, referred to the direct genetic manipulations on the human genome that haven't been typified in Venezuelan law, thus discovering a genetic biotechnology paradise.

  4. Epigenetic modulators of thyroid cancer.

    Science.gov (United States)

    Rodríguez-Rodero, Sandra; Delgado-Álvarez, Elías; Díaz-Naya, Lucía; Martín Nieto, Alicia; Menéndez Torre, Edelmiro

    2017-01-01

    There are some well known factors involved in the etiology of thyroid cancer, including iodine deficiency, radiation exposure at early ages, or some genetic changes. However, epigenetic modulators that may contribute to development of these tumors and be helpful to for both their diagnosis and treatment have recently been discovered. The currently known changes in DNA methylation, histone modifications, and non-coding RNAs in each type of thyroid carcinoma are reviewed here. Copyright © 2016 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

  5. CTCF Prevents the Epigenetic Drift of EBV Latency Promoter Qp

    Science.gov (United States)

    Tempera, Italo; Wiedmer, Andreas; Dheekollu, Jayaraju; Lieberman, Paul M.

    2010-01-01

    The establishment and maintenance of Epstein-Barr Virus (EBV) latent infection requires distinct viral gene expression programs. These gene expression programs, termed latency types, are determined largely by promoter selection, and controlled through the interplay between cell-type specific transcription factors, chromatin structure, and epigenetic modifications. We used a genome-wide chromatin-immunoprecipitation (ChIP) assay to identify epigenetic modifications that correlate with different latency types. We found that the chromatin insulator protein CTCF binds at several key regulatory nodes in the EBV genome and may compartmentalize epigenetic modifications across the viral genome. Highly enriched CTCF binding sites were identified at the promoter regions upstream of Cp, Wp, EBERs, and Qp. Since Qp is essential for long-term maintenance of viral genomes in type I latency and epithelial cell infections, we focused on the role of CTCF in regulating Qp. Purified CTCF bound ∼40 bp upstream of the EBNA1 binding sites located at +10 bp relative to the transcriptional initiation site at Qp. Mutagenesis of the CTCF binding site in EBV bacmids resulted in a decrease in the recovery of stable hygromycin-resistant episomes in 293 cells. EBV lacking the Qp CTCF site showed a decrease in Qp transcription initiation and a corresponding increase in Cp and Fp promoter utilization at 8 weeks post-transfection. However, by 16 weeks post-transfection, bacmids lacking CTCF sites had no detectable Qp transcription and showed high levels of histone H3 K9 methylation and CpG DNA methylation at the Qp initiation site. These findings provide direct genetic evidence that CTCF functions as a chromatin insulator that prevents the promiscuous transcription of surrounding genes and blocks the epigenetic silencing of an essential promoter, Qp, during EBV latent infection. PMID:20730088

  6. Epigenetic regulation of ageing: linking environmental inputs to genomic stability

    Science.gov (United States)

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

    2016-01-01

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

  7. Legislation on direct-to-consumer genetic testing in seven European countries.

    Science.gov (United States)

    Borry, Pascal; van Hellemondt, Rachel E; Sprumont, Dominique; Jales, Camilla Fittipaldi Duarte; Rial-Sebbag, Emmanuelle; Spranger, Tade Matthias; Curren, Liam; Kaye, Jane; Nys, Herman; Howard, Heidi

    2012-07-01

    An increasing number of private companies are now offering direct-to-consumer (DTC) genetic testing services. Although a lot of attention has been devoted to the regulatory framework of DTC genetic testing services in the USA, only limited information about the regulatory framework in Europe is available. We will report on the situation with regard to the national legislation on DTC genetic testing in seven European countries (Belgium, the Netherlands, Switzerland, Portugal, France, Germany, the United Kingdom). The paper will address whether these countries have legislation that specifically address the issue of DTC genetic testing or have relevant laws that is pertinent to the regulatory control of these services in their countries. The findings show that France, Germany, Portugal and Switzerland have specific legislation that defines that genetic tests can only be carried out by a medical doctor after the provision of sufficient information concerning the nature, meaning and consequences of the genetic test and after the consent of the person concerned. In the Netherlands, some DTC genetic tests could fall under legislation that provides the Minister the right to refuse to provide a license to operate if a test is scientifically unsound, not in accordance with the professional medical practice standards or if the expected benefit is not in balance with the (potential) health risks. Belgium and the United Kingdom allow the provision of DTC genetic tests.

  8. Trends and Gaps in Awareness of Direct-to-Consumer Genetic Tests From 2007 to 2014.

    Science.gov (United States)

    Apathy, Nate C; Menser, Terri; Keeran, Lindsay M; Ford, Eric W; Harle, Christopher A; Huerta, Timothy R

    2018-06-01

    Direct-to-consumer genetic tests for inherited disease risks have gained recent approvals from the Food and Drug Administration, and interest in these tests has continued to grow. Broad use of these tests coupled with planning and discussion with health providers regarding genetic risks and potential protective behavior changes have been proposed as preventive tools to reduce health disparities and improve equity in health outcomes. However, awareness of direct-to-consumer genetic testing has historically demonstrated differences by education, income, and race; these disparities could jeopardize potential benefits by limiting access and use. The national survey data from the Health Information National Trends Survey was analyzed to understand how overall awareness of direct-to-consumer genetic testing and disparities in awareness across sociodemographic groups have changed since 2007. The findings showed persistent disparities, as well as a widening gap in awareness between Hispanics and non-Hispanic whites (OR 2007 =1.52, OR 2014 =0.58, p change =0.0056), despite overall increases in awareness over time. Given these findings, policies regulating direct-to-consumer genetic tests should prioritize equitable distribution of benefits by including provisions that counteract prevailing disparities in awareness. Copyright © 2018 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  9. Epigenetic memory in mammals

    Directory of Open Access Journals (Sweden)

    Zoe eMigicovsky

    2011-06-01

    Full Text Available Epigenetic information can be passed on from one generation to another via DNA methylation, histone modifications and changes in small RNAs, a process called epigenetic memory. During a mammal’s lifecycle epigenetic reprogramming, or the resetting of most epigenetic marks, occurs twice. The first instance of reprogramming occurs in primordial germ cells and the second occurs following fertilization. These processes may be both passive and active. In order for epigenetic inheritance to occur the epigenetic modifications must be able to escape reprogramming. There are several examples supporting this non-Mendelian mechanism of inheritance including the prepacking of early developmental genes in histones instead of protamines in sperm, genomic imprinting via methylation marks, the retention of CenH3 in mammalian sperm and the inheritance of piwi-associated interfering RNAs. The ability of mammals to pass on epigenetic information to their progeny provides clear evidence that inheritance is not restricted to DNA sequence and epigenetics plays a key role in producing viable offspring.

  10. CROSSOVERS BETWEEN EPIGENESIS AND EPIGENETICS. A MULTICENTER APPROACH TO THE HISTORY OF EPIGENETICS (1901-1975).

    Science.gov (United States)

    Costa, Rossella; Frezza, Giulia

    2014-01-01

    The origin of epigenetics has been traditionally traced back to Conrad Hal Waddington's foundational work in 1940s. The aim of the present paper is to reveal a hidden history of epigenetics, by means of a multicenter approach. Our analysis shows that genetics and embryology in early XX century--far from being non-communicating vessels--shared similar questions, as epitomized by Thomas Hunt Morgan's works. Such questions were rooted in the theory of epigenesis and set the scene for the development of epigenetics. Since the 1950s, the contribution of key scientists (Mary Lyon and Eduardo Scarano), as well as the discussions at the international conference of Gif-sur-Yvette (1957) paved the way for three fundamental shifts of focus: 1. From the whole embryo to the gene; 2. From the gene to the complex extranuclear processes of development; 3. From cytoplasmic inheritance to the epigenetics mechanisms.

  11. Investigating core genetic-and-epigenetic cell cycle networks for stemness and carcinogenic mechanisms, and cancer drug design using big database mining and genome-wide next-generation sequencing data.

    Science.gov (United States)

    Li, Cheng-Wei; Chen, Bor-Sen

    2016-10-01

    Recent studies have demonstrated that cell cycle plays a central role in development and carcinogenesis. Thus, the use of big databases and genome-wide high-throughput data to unravel the genetic and epigenetic mechanisms underlying cell cycle progression in stem cells and cancer cells is a matter of considerable interest. Real genetic-and-epigenetic cell cycle networks (GECNs) of embryonic stem cells (ESCs) and HeLa cancer cells were constructed by applying system modeling, system identification, and big database mining to genome-wide next-generation sequencing data. Real GECNs were then reduced to core GECNs of HeLa cells and ESCs by applying principal genome-wide network projection. In this study, we investigated potential carcinogenic and stemness mechanisms for systems cancer drug design by identifying common core and specific GECNs between HeLa cells and ESCs. Integrating drug database information with the specific GECNs of HeLa cells could lead to identification of multiple drugs for cervical cancer treatment with minimal side-effects on the genes in the common core. We found that dysregulation of miR-29C, miR-34A, miR-98, and miR-215; and methylation of ANKRD1, ARID5B, CDCA2, PIF1, STAMBPL1, TROAP, ZNF165, and HIST1H2AJ in HeLa cells could result in cell proliferation and anti-apoptosis through NFκB, TGF-β, and PI3K pathways. We also identified 3 drugs, methotrexate, quercetin, and mimosine, which repressed the activated cell cycle genes, ARID5B, STK17B, and CCL2, in HeLa cells with minimal side-effects.

  12. Epigenetic mechanisms in the initiation of hematological malignancies

    Directory of Open Access Journals (Sweden)

    Ali Maleki

    2011-10-01

    Full Text Available Background: Cancer development is not restricted to the genetic changes, but also to epigenetic changes. Epigenetic processes are very important in the development of hematological malignancies. The main epigenetic alterations are aberrations in DNA methylation, post-translational modifications of histones, chromatin remodeling and microRNAs patterns, and these are associated with tumor genesis. All the various cellular pathways contributing to the neoplastic phenotype are affected by epigenetic genes in cancer. These pathways can be explored as biomarkers in clinical use for early detection of disease, malignancy classification and response to treatment with classical chemotherapy agents and epigenetic drugs. Materials and Method: A literature review was performed using PUBMED from 1985 to 2008. Cross referencing of discovered articles was also reviewed.Results: In chronic lymphocytic leukemia, regional hypermethylation of gene promoters leads to gene silencing. Many of these genes have tumor suppressor phenotypes. In myelodysplastic syndrome (MDS, CDKN2B (alias, P15, a cyclin-dependent kinase inhibitor that negatively regulates the cell cycle, has been shown to be hypermethylated in marrow stem (CD34+ cells in patients with MDS. At present both Vidaza and Decitabine (DNA methyltransferase inhibitors are approved for the treatment of MDS.Conclusion: Unlike mutations or deletions, DNA hypermethylation and histone deacetylation are potentially reversible by pharmacological inhibition, therefore those epigenetic changes have been recognized as promising novel therapeutic targets in hematopoietic malignances. In this review, we discussed molecular mechanisms of epigenetics, epigenetic changes in hematological malignancies and epigenetic based treatments

  13. Dad's Snoring May Have Left Molecular Scars in Your DNA: the Emerging Role of Epigenetics in Sleep Disorders.

    Science.gov (United States)

    Morales-Lara, Daniela; De-la-Peña, Clelia; Murillo-Rodríguez, Eric

    2018-04-01

    The sleep-wake cycle is a biological phenomena under the orchestration of neurophysiological, neurochemical, neuroanatomical, and genetical mechanisms. Moreover, homeostatic and circadian processes participate in the regulation of sleep across the light-dark period. Further complexity of the understanding of the genesis of sleep engages disturbances which have been characterized and classified in a variety of sleep-wake cycle disorders. The most prominent sleep alterations include insomnia as well as excessive daytime sleepiness. On the other side, several human diseases have been linked with direct changes in DNA, such as chromatin configuration, genomic imprinting, DNA methylation, histone modifications (acetylation, methylation, ubiquitylation or sumoylation, etc.), and activating RNA molecules that are transcribed from DNA but not translated into proteins. Epigenetic theories primarily emphasize the interaction between the environment and gene expression. According to these approaches, the environment to which mammals are exposed has a significant role in determining the epigenetic modifications occurring in chromosomes that ultimately would influence not only development but also the descendants' physiology and behavior. Thus, what makes epigenetics intriguing is that, unlike genetic variation, modifications in DNA are altered directly by the environment and, in some cases, these epigenetic changes may be inherited by future generations. Thus, it is likely that epigenetic phenomena might contribute to the homeostatic and/or circadian control of sleep and, possibly, have an undescribed link with sleep disorders. An exciting new horizon of research is arising between sleep and epigenetics since it represents the relevance of the study of how the genome learns from its experiences and modulates behavior, including sleep.

  14. [Epigenetic alterations in acute lymphoblastic leukemia].

    Science.gov (United States)

    Navarrete-Meneses, María Del Pilar; Pérez-Vera, Patricia

    Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. It is well-known that genetic alterations constitute the basis for the etiology of ALL. However, genetic abnormalities are not enough for the complete development of the disease, and additional alterations such as epigenetic modifications are required. Such alterations, like DNA methylation, histone modifications, and noncoding RNA regulation have been identified in ALL. DNA hypermethylation in promoter regions is one of the most frequent epigenetic modifications observed in ALL. This modification frequently leads to gene silencing in tumor suppressor genes, and in consequence, contributes to leukemogenesis. Alterations in histone remodeling proteins have also been detected in ALL, such as the overexpression of histone deacetylases enzymes, and alteration of acetyltransferases and methyltransferases. ALL also shows alteration in the expression of miRNAs, and in consequence, the modification in the expression of their target genes. All of these epigenetic modifications are key events in the malignant transformation since they lead to the deregulation of oncogenes as BLK, WNT5B and WISP1, and tumor suppressors such as FHIT, CDKN2A, CDKN2B, and TP53, which alter fundamental cellular processes and potentially lead to the development of ALL. Both genetic and epigenetic alterations contribute to the development and evolution of ALL. Copyright © 2017 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

  15. You want to do what? My mother's choice to have direct-to-consumer genetic testing.

    Science.gov (United States)

    Varga, Elizabeth A

    2012-06-01

    As a genetic counselor, I had mixed opinions when my mother told me of her intent to undergo genomewide, SNP-based direct-to-consumer (DTC) genetic testing. I cautioned her that results could be misleading, could increase anxiety and were often of limited clinical validity or utility. I warned of the possibility of learning unintended health information and expressed concerns about how the information might be used by a private company. I told her about the variability in results among companies. Yet, she persisted in her desire, reminding me that she was an informed consumer. After reviewing her goals and understanding of the information she might receive, she elected to proceed. Despite my insistence that I would not be her personal genetic counselor, when the results came back, I found myself immersed in her genetic data. In this manuscript, I will examine how this personal experience challenged my perceptions of DTC testing.

  16. "Be ready against cancer, now": direct-to-consumer advertising for genetic testing.

    Science.gov (United States)

    William-Jones, Bryn

    2006-04-01

    A recent addition to the debate about the benefits and harms of direct-to-consumer (DTC) advertising of medicines and pharmaceuticals is a growing critique of DTC marketing and sale of genetic tests. Academic and policy literatures exploring this issue have, however, tended to focus on the sale of genetic tests, paying rather less attention to the particular implications of advertising. The globalization of broadcast media and ever increasing access to the Internet mean that public exposure to advertising for medical technologies is a reality that national regulatory bodies will be hard pressed to constrain. Working through a case study detailing Myriad Genetics' 2002 pilot advertising campaign for their BRACAnalysis genetic susceptibility test for hereditary breast and ovarian cancer, this paper highlights some of the diverse and often overlooked and unregulated approaches to DTC advertising, and the associated social, ethical and policy implications.

  17. Evaluating online direct-to-consumer marketing of genetic tests: informed choices or buyers beware?

    Science.gov (United States)

    Geransar, Rose; Einsiedel, Edna

    2008-03-01

    Commercialization of genetic technologies is expanding the horizons for the marketing and sales of genetic tests direct-to-consumers (DTCs). This study assesses the information provision and access requirements that are in place for genetic tests that are being advertised DTC over the Internet. Sets of key words specific to DTC genetic testing were entered into popular Internet search engines to generate a list of 24 companies engaging in DTC advertising. Company requirements for physician mediation, genetic counseling arrangements, and information provision were coded to develop categories for quantitative analysis within each variable. Results showed that companies offering risk assessment and diagnostic testing were most likely to require that testing be mediated by a clinician, and to recommend physician-arranged counseling. Companies offering enhancement testing were less likely to require physician mediation of services and more likely to provide long-distance genetic counseling. DTC advertisements often provided information on disease etiology; this was most common in the case of multifactorial diseases. The majority of companies cited outside sources to support the validity of claims about clinical utility of the tests being advertised; companies offering risk assessment tests most frequently cited all information sources. DTC advertising for genetic tests that lack independent professional oversight raises troubling questions about appropriate use and interpretation of these tests by consumers and carries implications for the standards of patient care. These implications are discussed in the context of a public healthcare system.

  18. Epigenetic regulation of hematopoietic stem cell aging

    International Nuclear Information System (INIS)

    Beerman, Isabel; Rossi, Derrick J.

    2014-01-01

    Aging is invariably associated with alterations of the hematopoietic stem cell (HSC) compartment, including loss of functional capacity, altered clonal composition, and changes in lineage contribution. Although accumulation of DNA damage occurs during HSC aging, it is unlikely such consistent aging phenotypes could be solely attributed to changes in DNA integrity. Another mechanism by which heritable traits could contribute to the changes in the functional potential of aged HSCs is through alterations in the epigenetic landscape of adult stem cells. Indeed, recent studies on hematopoietic stem cells have suggested that altered epigenetic profiles are associated with HSC aging and play a key role in modulating the functional potential of HSCs at different stages during ontogeny. Even small changes of the epigenetic landscape can lead to robustly altered expression patterns, either directly by loss of regulatory control or through indirect, additive effects, ultimately leading to transcriptional changes of the stem cells. Potential drivers of such changes in the epigenetic landscape of aged HSCs include proliferative history, DNA damage, and deregulation of key epigenetic enzymes and complexes. This review will focus largely on the two most characterized epigenetic marks – DNA methylation and histone modifications – but will also discuss the potential role of non-coding RNAs in regulating HSC function during aging

  19. Transgenerational epigenetic effects on animal behaviour.

    Science.gov (United States)

    Jensen, Per

    2013-12-01

    Over the last decade a shift in paradigm has occurred with respect to the interaction between environment and genes. It is now clear that animal genomes are regulated to a large extent as a result of input from environmental events and experiences, which cause short- and long-term modifications in epigenetic markings of DNA and histones. In this review, the evidence that such epigenetic modifications can affect the behaviour of animals is explored, and whether such acquired behaviour alterations can transfer across generation borders. First, the mechanisms by which experiences cause epigenetic modifications are examined. This includes, for example, methylation of cytosine in CpG positions and acetylation of histones, and studies showing that this can be modified by early experiences. Secondly, the evidence that specific modifications in the epigenome can be the cause of behaviour variation is reviewed. Thirdly, the extent to which this phenotypically active epigenetic variants can be inherited either through the germline or through reoccurring environmental conditions is examined. A particularly interesting observation is that epigenetic modifications are often linked to stress, and may possibly be mediated by steroid effects. Finally, the idea that transgenerationally stable epigenetic variants may serve as substrates for natural selection is explored, and it is speculated that they may even predispose for directed, non-random mutations. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Epigenetic regulation of hematopoietic stem cell aging

    Energy Technology Data Exchange (ETDEWEB)

    Beerman, Isabel, E-mail: isabel.beerman@childrens.harvard.edu [Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138 (United States); Department of Pediatrics, Harvard Medical School, Boston, MA 02115 (United States); Program in Cellular and Molecular Medicine, Division of Hematology/Oncology, Boston Children' s Hospital, MA 02116 (United States); Rossi, Derrick J. [Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138 (United States); Department of Pediatrics, Harvard Medical School, Boston, MA 02115 (United States); Program in Cellular and Molecular Medicine, Division of Hematology/Oncology, Boston Children' s Hospital, MA 02116 (United States)

    2014-12-10

    Aging is invariably associated with alterations of the hematopoietic stem cell (HSC) compartment, including loss of functional capacity, altered clonal composition, and changes in lineage contribution. Although accumulation of DNA damage occurs during HSC aging, it is unlikely such consistent aging phenotypes could be solely attributed to changes in DNA integrity. Another mechanism by which heritable traits could contribute to the changes in the functional potential of aged HSCs is through alterations in the epigenetic landscape of adult stem cells. Indeed, recent studies on hematopoietic stem cells have suggested that altered epigenetic profiles are associated with HSC aging and play a key role in modulating the functional potential of HSCs at different stages during ontogeny. Even small changes of the epigenetic landscape can lead to robustly altered expression patterns, either directly by loss of regulatory control or through indirect, additive effects, ultimately leading to transcriptional changes of the stem cells. Potential drivers of such changes in the epigenetic landscape of aged HSCs include proliferative history, DNA damage, and deregulation of key epigenetic enzymes and complexes. This review will focus largely on the two most characterized epigenetic marks – DNA methylation and histone modifications – but will also discuss the potential role of non-coding RNAs in regulating HSC function during aging.

  1. Epigenetic drift in the aging genome

    DEFF Research Database (Denmark)

    Tan, Qihua; Heijmans, Bastiaan T; Hjelmborg, Jacob V B

    2016-01-01

    for 10 years (age at intake 73-82 years). Biological pathway analysis and survival analysis were also conducted on CpGs showing longitudinal change in their DNA-methylation levels. Classical twin models were fitted to each CpG site to estimate the genetic and environmental effects on DNA...... × 10-07. Pathway analysis of genes linked to these CpGs identified biologically meaningful gene-sets involved in cellular-signalling events and in transmission across chemical synapses, which are important molecular underpinnings of aging-related degenerative disorders. CONCLUSION: Our epigenome......BACKGROUND: Current epigenetic studies on aging are dominated by the cross-sectional design that correlates subjects' ages or age groups with their measured epigenetic profiles. Such studies have been more aimed at age prediction or building up the epigenetic clock of age rather than focusing...

  2. Exploiting Epigenetic Alterations in Prostate Cancer.

    Science.gov (United States)

    Baumgart, Simon J; Haendler, Bernard

    2017-05-09

    Prostate cancer affects an increasing number of men worldwide and is a leading cause of cancer-associated deaths. Beside genetic mutations, many epigenetic alterations including DNA and histone modifications have been identified in clinical prostate tumor samples. They have been linked to aberrant activity of enzymes and reader proteins involved in these epigenetic processes, leading to the search for dedicated inhibitory compounds. In the wake of encouraging anti-tumor efficacy results in preclinical models, epigenetic modulators addressing different targets are now being tested in prostate cancer patients. In addition, the assessment of microRNAs as stratification biomarkers, and early clinical trials evaluating suppressor microRNAs as potential prostate cancer treatment are being discussed.

  3. Exploiting Epigenetic Alterations in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Simon J. Baumgart

    2017-05-01

    Full Text Available Prostate cancer affects an increasing number of men worldwide and is a leading cause of cancer-associated deaths. Beside genetic mutations, many epigenetic alterations including DNA and histone modifications have been identified in clinical prostate tumor samples. They have been linked to aberrant activity of enzymes and reader proteins involved in these epigenetic processes, leading to the search for dedicated inhibitory compounds. In the wake of encouraging anti-tumor efficacy results in preclinical models, epigenetic modulators addressing different targets are now being tested in prostate cancer patients. In addition, the assessment of microRNAs as stratification biomarkers, and early clinical trials evaluating suppressor microRNAs as potential prostate cancer treatment are being discussed.

  4. Epigenetic variation in mangrove plants occurring in contrasting natural environment.

    Directory of Open Access Journals (Sweden)

    Catarina Fonseca Lira-Medeiros

    2010-04-01

    Full Text Available Epigenetic modifications, such as cytosine methylation, are inherited in plant species and may occur in response to biotic or abiotic stress, affecting gene expression without changing genome sequence. Laguncularia racemosa, a mangrove species, occurs in naturally contrasting habitats where it is subjected daily to salinity and nutrient variations leading to morphological differences. This work aims at unraveling how CpG-methylation variation is distributed among individuals from two nearby habitats, at a riverside (RS or near a salt marsh (SM, with different environmental pressures and how this variation is correlated with the observed morphological variation.Significant differences were observed in morphological traits such as tree height, tree diameter, leaf width and leaf area between plants from RS and SM locations, resulting in smaller plants and smaller leaf size in SM plants. Methyl-Sensitive Amplified Polymorphism (MSAP was used to assess genetic and epigenetic (CpG-methylation variation in L. racemosa genomes from these populations. SM plants were hypomethylated (14.6% of loci had methylated samples in comparison to RS (32.1% of loci had methylated samples. Within-population diversity was significantly greater for epigenetic than genetic data in both locations, but SM also had less epigenetic diversity than RS. Frequency-based (G(ST and multivariate (beta(ST methods that estimate population structure showed significantly greater differentiation among locations for epigenetic than genetic data. Co-Inertia analysis, exploring jointly the genetic and epigenetic data, showed that individuals with similar genetic profiles presented divergent epigenetic profiles that were characteristic of the population in a particular environment, suggesting that CpG-methylation changes may be associated with environmental heterogeneity.In spite of significant morphological dissimilarities, individuals of L. racemosa from salt marsh and riverside presented

  5. Learning epigenetic regulation from mycobacteria

    Directory of Open Access Journals (Sweden)

    Sanjeev Khosla

    2016-01-01

    Full Text Available In a eukaryotic cell, the transcriptional fate of a gene is determined by the profile of the epigenetic modifications it is associated with and the conformation it adopts within the chromatin. Therefore, the function that a cell performs is dictated by the sum total of the chromatin organization and the associated epigenetic modifications of each individual gene in the genome (epigenome. As the function of a cell during development and differentiation is determined by its microenvironment, any factor that can alter this microenvironment should be able to alter the epigenome of a cell. In the study published in Nature Communications (Yaseen [2015] Nature Communications 6:8922 doi: 10.1038/ncomms9922, we show that pathogenic Mycobacterium tuberculosis has evolved strategies to exploit this pliability of the host epigenome for its own survival. We describe the identification of a methyltransferase from M. tuberculosis that functions to modulate the host epigenome by methylating a novel, non-canonical arginine, H3R42 in histone H3. In another study, we showed that the mycobacterial protein Rv2966c methylates cytosines present in non-CpG context within host genomic DNA upon infection. Proteins with ability to directly methylate host histones H3 at a novel lysine residue (H3K14 has also been identified from Legionella pnemophilia (RomA. All these studies indicate the use of non-canonical epigenetic mechanisms by pathogenic bacteria to hijack the host transcriptional machinery.

  6. Genetic variation in PCAF, a key mediator in epigenetics, is associated with reduced vascular morbidity and mortality: evidence for a new concept from three independent prospective studies

    NARCIS (Netherlands)

    Pons, D.; Trompet, S.; Craen, A.J.M.; Thijssen, P.E.; Quax, P.H.A.; de Vries, M.R.; Wierda, R.J.; van den Elsen, P.J.; Monraats, P.S.; Ewing, M.M.; Heijmans, B.T.; Slagboom, P.E.; Zwinderman, A.H.; Doevendans, P.A.F.M.; Tio, R.A.; de Winter, R.J.; de Maat, M.P.M.; Lakoubova, O.A.; Sattar, N.; Sheperd, J.; Westendorp, R.G.J.; Jukema, J.W.

    2011-01-01

    Aims: This study was designed to investigate the counterbalancing influence of genetic variation in the promoter of the gene encoding P300/CBP associated factor (PCAF), a lysine acetyltransferase (KAT), on coronary heart disease (CHD) and mortality. Methods and results: The association of genetic

  7. Direct-to-consumer genetic testing for predicting sports performance and talent identification: Consensus statement

    Science.gov (United States)

    Webborn, Nick; Williams, Alun; McNamee, Mike; Bouchard, Claude; Pitsiladis, Yannis; Ahmetov, Ildus; Ashley, Euan; Byrne, Nuala; Camporesi, Silvia; Collins, Malcolm; Dijkstra, Paul; Eynon, Nir; Fuku, Noriyuki; Garton, Fleur C; Hoppe, Nils; Holm, Søren; Kaye, Jane; Klissouras, Vassilis; Lucia, Alejandro; Maase, Kamiel; Moran, Colin; North, Kathryn N; Pigozzi, Fabio; Wang, Guan

    2015-01-01

    The general consensus among sport and exercise genetics researchers is that genetic tests have no role to play in talent identification or the individualised prescription of training to maximise performance. Despite the lack of evidence, recent years have witnessed the rise of an emerging market of direct-to-consumer marketing (DTC) tests that claim to be able to identify children's athletic talents. Targeted consumers include mainly coaches and parents. There is concern among the scientific community that the current level of knowledge is being misrepresented for commercial purposes. There remains a lack of universally accepted guidelines and legislation for DTC testing in relation to all forms of genetic testing and not just for talent identification. There is concern over the lack of clarity of information over which specific genes or variants are being tested and the almost universal lack of appropriate genetic counselling for the interpretation of the genetic data to consumers. Furthermore independent studies have identified issues relating to quality control by DTC laboratories with different results being reported from samples from the same individual. Consequently, in the current state of knowledge, no child or young athlete should be exposed to DTC genetic testing to define or alter training or for talent identification aimed at selecting gifted children or adolescents. Large scale collaborative projects, may help to develop a stronger scientific foundation on these issues in the future. PMID:26582191

  8. Attitudes about regulation among direct-to-consumer genetic testing customers.

    Science.gov (United States)

    Bollinger, Juli Murphy; Green, Robert C; Kaufman, David

    2013-05-01

    The first regulatory rulings by the U.S. Food and Drug Administration on direct-to-consumer (DTC) genetic testing services are expected soon. As the process of regulating these and other genetic tests moves ahead, it is important to understand the preferences of DTC genetic testing customers about the regulation of these products. An online survey of customers of three DTC genetic testing companies was conducted 2-8 months after they had received their results. Participants were asked about the importance of regulating the companies selling DTC genetic tests. Most of the 1,046 respondents responded that it would be important to have a nongovernmental (84%) or governmental agency (73%) monitor DTC companies' claims to ensure the consistency with scientific evidence. However, 66% also felt that it was important that DTC tests be available without governmental oversight. Nearly, all customers favored a policy to ensure that insurers and law enforcement officials could not access their information. Although many DTC customers want access to genetic testing services without restrictions imposed by the government regulation, most also favor an organization operating alongside DTC companies that will ensure that the claims made by the companies are consistent with sound scientific evidence. This seeming contradiction may indicate that DTC customers want to ensure that they have unfettered access to high-quality information. Additionally, policies to help ensure privacy of data would be welcomed by customers, despite relatively high confidence in the companies.

  9. Potential of Epigenetic Therapies in Non-cancerous Conditions

    Directory of Open Access Journals (Sweden)

    Raymond eYung

    2014-12-01

    Full Text Available There has been an explosion of knowledge in the epigenetics field in the past 20 years. The first epigenetic therapies have arrived in the clinic for cancer treatments. In contrast, much of the promise of epigenetic therapies for non-cancerous conditions remains in the laboratories. The current review will focus on the recent progress that has been made in understanding the pathogenic role of epigenetics in immune and inflammatory conditions, and how the knowledge may provide much needed new therapeutic targets for many autoimmune diseases. Dietary factors are increasingly recognized as potential modifiers of epigenetic marks that can influence health and diseases across generations. The current epigenomics revolution will almost certainly complement the explosion of personal genetics medicine to help guide treatment decisions and disease risk stratification.

  10. The Real Culprit in Systemic Lupus Erythematosus: Abnormal Epigenetic Regulation

    Science.gov (United States)

    Wu, Haijing; Zhao, Ming; Chang, Christopher; Lu, Qianjin

    2015-01-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organs and the presence of anti-nuclear antibodies. The pathogenesis of SLE has been intensively studied but remains far from clear. B and T lymphocyte abnormalities, dysregulation of apoptosis, defects in the clearance of apoptotic materials, and various genetic and epigenetic factors are attributed to the development of SLE. The latest research findings point to the association between abnormal epigenetic regulation and SLE, which has attracted considerable interest worldwide. It is the purpose of this review to present and discuss the relationship between aberrant epigenetic regulation and SLE, including DNA methylation, histone modifications and microRNAs in patients with SLE, the possible mechanisms of immune dysfunction caused by epigenetic changes, and to better understand the roles of aberrant epigenetic regulation in the initiation and development of SLE and to provide an insight into the related therapeutic options in SLE. PMID:25988383

  11. Whole Genome Epigenetics

    National Research Council Canada - National Science Library

    Carmell, Michelle A; Hannon, Gregory J

    2005-01-01

    .... Recently, several labs have published manuscripts identifying RNA interference as being crucial for the establishment of such epigenetic changes in species as diverse as Drosophila, plants, and the fission yeast S. pombe...

  12. Whole Genome Epigenetics

    National Research Council Canada - National Science Library

    Carmell, Michelle A; Hannon, Gregory J

    2004-01-01

    .... Recently, several labs have published manuscripts identifying RNA interference as being crucial for the establishment of such epigenetic changes in species as diverse as Drosophila, plants, and the fission yeast S. pombe...

  13. Whole Genome Epigenetics

    National Research Council Canada - National Science Library

    Carmell, Michelle

    2003-01-01

    .... Recently, several labs have published manuscripts identifying RNA interference as being crucial for the establishment of such epigenetic changes in species as diverse as Drosphilia, plants, and the fission yeast S. pombe...

  14. Whole Genome Epigenetics

    National Research Council Canada - National Science Library

    Carmell, Michelle A; Hannon, Gregory J

    2004-01-01

    .... However, this is only part of the picture. Increasingly, we are learning that epigenetic changes, that is, changes in chromatin structure, are critically important in regulating cellular gene expression...

  15. Whole Genome Epigenetics

    National Research Council Canada - National Science Library

    Carmell, Michelle A; Hannon, Gregory J

    2005-01-01

    .... However, this is only part of the picture. Increasingly, we are learning that epigenetic changes, that is, changes in chromatin structure, are critically important in regulating cellular gene expression...

  16. Whole Genome Epigenetics

    National Research Council Canada - National Science Library

    Carmell, Michelle

    2003-01-01

    .... However, this is only part of the picture. Increasingly, we are learning that epigenetic changes, that is, changes in chromatin structure, are critically important in regulation cellular gene expression...

  17. Nature, Nurture and Epigenetics

    Science.gov (United States)

    Crews, David; Gillette, Ross; Miller-Crews, Isaac; Gore, Andrea C.; Skinner, Michael K.

    2015-01-01

    Real life by definition combines heritability (e.g., the legacy of exposures) and experience (e.g. stress during sensitive or ‘critical’ periods), but how to study or even model this interaction has proven difficult. The hoary concept of evaluating traits according to nature vs. nurture continues to persist despite repeated demonstrations that it retards, rather than advances, our understanding of biological processes. Behavioral genetics has proven the obvious, that genes influences behavior and, vice versa, that behavior influences genes. The concept of Genes X Environment (G X E) and its modern variants was viewed as an improvement on nature-nurture but has proven that, except in rare instances, it is not possible to fractionate phenotypes into these constituent elements. The entanglement inherent in terms such as nature-nurture or GXE is a Gordian knot that cannot be dissected or even split. Given that the world today is not what it was less than a century ago, yet the arbitrator (differential survival and reproduction) has stayed constant, de novo principles and practices are needed to better predict what the future holds. Put simply, the transformation that is now occurring within and between individuals as a product of global endocrine disruption is quite independent of what has been regarded as evolution by selection. This new perspective should focus on how epigenetic modifications might revise approaches to understand how the phenotype and, in particular its components, is shaped. In this review we summarize the literature in this developing area, focusing on our research on the fungicide vinclozolin. PMID:25102229

  18. Nature, nurture and epigenetics.

    Science.gov (United States)

    Crews, David; Gillette, Ross; Miller-Crews, Isaac; Gore, Andrea C; Skinner, Michael K

    2014-12-01

    Real life by definition combines heritability (e.g., the legacy of exposures) and experience (e.g. stress during sensitive or 'critical' periods), but how to study or even model this interaction has proven difficult. The hoary concept of evaluating traits according to nature versus nurture continues to persist despite repeated demonstrations that it retards, rather than advances, our understanding of biological processes. Behavioral genetics has proven the obvious, that genes influence behavior and, vice versa, that behavior influences genes. The concept of Genes X Environment (G X E) and its modern variants was viewed as an improvement on nature-nurture but has proven that, except in rare instances, it is not possible to fractionate phenotypes into these constituent elements. The entanglement inherent in terms such as nature-nurture or G X E is a Gordian knot that cannot be dissected or even split. Given that the world today is not what it was less than a century ago, yet the arbitrator (differential survival and reproduction) has stayed constant, de novo principles and practices are needed to better predict what the future holds. Put simply, the transformation that is now occurring within and between individuals as a product of global endocrine disruption is quite independent of what has been regarded as evolution by selection. This new perspective should focus on how epigenetic modifications might revise approaches to understand how the phenotype and, in particular its components, is shaped. In this review we summarize the literature in this developing area, focusing on our research on the fungicide vinclozolin. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  19. Epigenetics and Cellular Metabolism

    OpenAIRE

    Wenyi Xu; Fengzhong Wang; Zhongsheng Yu; Fengjiao Xin

    2016-01-01

    Living eukaryotic systems evolve delicate cellular mechanisms for responding to various environmental signals. Among them, epigenetic machinery (DNA methylation, histone modifications, microRNAs, etc.) is the hub in transducing external stimuli into transcriptional response. Emerging evidence reveals the concept that epigenetic signatures are essential for the proper maintenance of cellular metabolism. On the other hand, the metabolite, a main environmental input, can also influence the proce...

  20. Epigenetics in Prostate Cancer

    OpenAIRE

    Albany, Costantine; Alva, Ajjai S.; Aparicio, Ana M.; Singal, Rakesh; Yellapragada, Sarvari; Sonpavde, Guru; Hahn, Noah M.

    2011-01-01

    Prostate cancer (PC) is the most commonly diagnosed nonskin malignancy and the second most common cause of cancer death among men in the United States. Epigenetics is the study of heritable changes in gene expression caused by mechanisms other than changes in the underlying DNA sequences. Two common epigenetic mechanisms, DNA methylation and histone modification, have demonstrated critical roles in prostate cancer growth and metastasis. DNA hypermethylation of cytosine-guanine (CpG) rich sequ...

  1. An ENU mutagenesis screen identifies novel and known genes involved in epigenetic processes in the mouse

    Czech Academy of Sciences Publication Activity Database

    Daxinger, L.; Harten, S.K.; Oey, H.; Epp, Trevor; Isbel, L.; Huang, E.; Whitelaw, N.; Apedaile, A.; Sorolla, A.; Yong, J.; Bharti, V.; Sutton, J.; Ashe, A.; Pang, Z.Y.; Wallace, N.; Gerhardt, D.J.; Blewitt, M.E.; Jeddeloh, J.A.; Whitelaw, E.

    2013-01-01

    Roč. 14, č. 9 (2013) ISSN 1465-6906 Institutional support: RVO:68378050 Keywords : epigenetics * variegation * forward genetics Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 10.465, year: 2013

  2. [Epigenetics 2.0: The multiple faces of the genome].

    Science.gov (United States)

    Rubinstein, Marcelo

    2016-09-01

    Epigenetics is the branch of genetics that studies the dynamic relationship between stable genotypes and varying phenotypes. To this end, epigenetics aims to discover the molecular mechanisms that explain how different nutrients and hormones, environmental changes, and emotional, social and cognitive experiences modify gene expression and behaviors, even permanently so. Psychiatry has learned that diseases with strong genetic predisposition, such as schizophrenia, show a concordance of around 50% between monozygotic twins, thus evidencing the importance of the genetic background and the presence of environmental variables that stimulate or block phenotypic development. The interest in epigenetics has increased during the last few years due to fundamental discoveries made in molecular and behavioral genetics, although within this framework factual knowledge coexists with fictional expectations and wrong concepts. Is it possible that epigenetic variants modify temperament and human behavior? May abused or neglected children develop long-lasting epigenetic marks in their DNA? May bipolar states correlate with different epigenetic signatures? Studying these subjects in not an easy task, but experiments performed in lab animals suggest that these conjectures are reasonable, although there is still a long distance between hypotheses and scientifically proven facts.

  3. The expanding role of epigenetics in the development, diagnosis and treatment of prostate cancer and benign prostatic hyperplasia.

    Science.gov (United States)

    Dobosy, Joseph R; Roberts, J Lea W; Fu, Vivian X; Jarrard, David F

    2007-03-01

    the prostate to developing cancer. Treatments involving 5-aza-deoxycytosine and other, more selective DNA methyltransferase inhibitors remove methyl residues from silenced genes, generating re-expression, and are currently being used in therapeutic trials. Histone deacetylase inhibitors have shown promise, not only by directly reactivating silenced genes, but also as regulators of apoptosis and sensitizers to radiation therapy. Evolving data support a significant role for epigenetic processes in the development of prostate cancer and benign prostatic hyperplasia. Epigenetic changes can predict tumor behavior and often distinguish between genetically identical tumors. Targeted drugs that alter epigenetic modifications hold promise as a tool for curing and preventing these diseases.

  4. IBM1, a JmjC domain-containing histone demethylase, is involved in the regulation of RNA-directed DNA methylation through the epigenetic control of RDR2 and DCL3 expression in Arabidopsis

    Science.gov (United States)

    Fan, Di; Dai, Yan; Wang, Xuncheng; Wang, Zhenjie; He, Hang; Yang, Hongchun; Cao, Ying; Deng, Xing Wang; Ma, Ligeng

    2012-01-01

    Small RNA-directed DNA methylation (RdDM) is an important epigenetic pathway in Arabidopsis that controls the expression of multiple genes and several developmental processes. RNA-DEPENDENT RNA POLYMERASE 2 (RDR2) and DICER-LIKE 3 (DCL3) are necessary factors in 24-nt small interfering RNA (siRNA) biogenesis, which is part of the RdDM pathway. Here, we found that Increase in BONSAI Methylation 1 (IBM1), a conserved JmjC family histone demethylase, is directly associated with RDR2 and DCL3 chromatin. The mutation of IBM1 induced the hypermethylation of H3K9 and DNA non-CG sites within RDR2 and DCL3, which repressed their expression. A genome-wide analysis suggested that the reduction in RDR2 and DCL3 expression affected siRNA biogenesis in a locus-specific manner and disrupted RdDM-directed gene repression. Together, our results suggest that IBM1 regulates gene expression through two distinct pathways: direct association to protect genes from silencing by preventing the coupling of histone and DNA methylation, and indirect silencing of gene expression through RdDM-directed repression. PMID:22772985

  5. A genetic link between epigenetic repressor AS1-AS2 and a putative small subunit processome in leaf polarity establishment of Arabidopsis

    Directory of Open Access Journals (Sweden)

    Yoko Matsumura

    2016-07-01

    Full Text Available Although the DEAD-box RNA helicase family is ubiquitous in eukaryotes, its developmental role remains unelucidated. Here, we report that cooperative action between the Arabidopsis nucleolar protein RH10, an ortholog of human DEAD-box RNA helicase DDX47, and the epigenetic repressor complex of ASYMMETRIC-LEAVES1 (AS1 and AS2 (AS1-AS2 is critical to repress abaxial (ventral genes ETT/ARF3 and ARF4, which leads to adaxial (dorsal development in leaf primordia at shoot apices. Double mutations of rh10-1 and as2 (or as1 synergistically up-regulated the abaxial genes, which generated abaxialized filamentous leaves with loss of the adaxial domain. DDX47 is part of the small subunit processome (SSUP that mediates rRNA biogenesis. In rh10-1 we found various defects in SSUP-related events, such as: accumulation of 35S/33S rRNA precursors; reduction in the 18S/25S ratio; and nucleolar hypertrophy. Double mutants of as2 with mutations of genes that encode other candidate SSUP-related components such as nucleolin and putative rRNA methyltransferase exhibited similar synergistic defects caused by up-regulation of ETT/ARF3 and ARF4. These results suggest a tight link between putative SSUP and AS1-AS2 in repression of the abaxial-determining genes for cell fate decisions for adaxial development.

  6. Epigenetics and Child Psychiatry: Ethical and Legal Issues.

    Science.gov (United States)

    Thomas, Christopher R

    2015-10-01

    Epigenetics has the potential to revolutionize diagnosis and treatment in psychiatry, especially child psychiatry, as it may offer the opportunity for early detection and prevention, as well as development of new treatments. As with the previous introduction of genetic research in psychiatry, there is also the problem of unrealistic expectations and new legal and ethical problems. This article reviews the potential contributions and problems of epigenetic research in child psychiatry. Previous legal and ethical issues in genetic research serve as a guide to those in epigenetic research. Recommendations for safeguards and guidelines on the use of epigenetics with children and adolescents are outlined based on the identified issues. Copyright © 2015 John Wiley & Sons, Ltd.

  7. The epigenetic switches for neural development and psychiatric disorders.

    Science.gov (United States)

    Lv, Jingwen; Xin, Yongjuan; Zhou, Wenhao; Qiu, Zilong

    2013-07-20

    The most remarkable feature of the nervous system is that the development and functions of the brain are largely reshaped by postnatal experiences, in joint with genetic landscapes. The nature vs. nurture argument reminds us that both genetic and epigenetic information is indispensable for the normal function of the brain. The epigenetic regulatory mechanisms in the central nervous system have been revealed over last a decade. Moreover, the mutations of epigenetic modulator genes have been shown to be implicated in neuropsychiatric disorders, such as autism spectrum disorders. The epigenetic study has initiated in the neuroscience field for a relative short period of time. In this review, we will summarize recent discoveries about epigenetic regulation on neural development, synaptic plasticity, learning and memory, as well as neuropsychiatric disorders. Although the comprehensive view of how epigenetic regulation contributes to the function of the brain is still not completed, the notion that brain, the most complicated organ of organisms, is profoundly shaped by epigenetic switches is widely accepted. Copyright © 2013. Published by Elsevier Ltd.

  8. Direct to consumer genetic testing and the libertarian right to test.

    Science.gov (United States)

    Loi, Michele

    2016-09-01

    I sketch a libertarian argument for the right to test in the context of 'direct to consumer' (DTC) genetic testing. A libertarian right to genetic tests, as defined here, relies on the idea of a moral right to self-ownership. I show how a libertarian right to test can be inferred from this general libertarian premise, at least as a prima facie right, shifting the burden of justification on regulators. I distinguish this distinctively libertarian position from some arguments based on considerations of utility or autonomy, which are sometimes labelled 'libertarian' because they oppose a tight regulation of the direct to consumer genetic testing sector. If one takes the libertarian right to test as a starting point, the whole discussion concerning autonomy and personal utility may be sidestepped. Finally, I briefly consider some considerations that justify the regulation of the DTC genetic testing market, compatible with the recognition of a prima facie right to test. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  9. Autobiologies on YouTube: Narratives of Direct-to-Consumer Genetic Testing

    Science.gov (United States)

    Harris, Anna; Kelly, Susan E.; Wyatt, Sally

    2014-01-01

    Despite a growing personal genomics market, little is known about how people engage with the possibilities offered by direct-to-consumer (DTC) genetic testing. In order to help address this gap, this study deploys narrative analysis of YouTube videos posted by individuals who have purchased DTC genetic testing for disease. Genetic testing is said to be contributing to new states of illness, where individuals may become “patients-in-waiting.” In the videos analyzed, we found a new form of storytelling about this ambiguous state of illness, which we refer to as autobiology. Autobiology – the study of, and story about, one's own biology – concerns narratives of sense-making through forms of biological practice, as well as wayfaring narratives which interweave genetic markers and family histories of disease. These autobiologies – part of a broader shift toward public stories about genetics and other healthcare technologies – exhibit playfulness, as well as being bound with consumerist practices. PMID:24772003

  10. Exploring dispositional tendencies to seek online information about direct-to-consumer genetic testing.

    Science.gov (United States)

    Paquin, Ryan S; Richards, Adam S; Koehly, Laura M; McBride, Colleen M

    2012-12-01

    Varying perspectives exist regarding the implications of genetic susceptibility testing for common disease, with some anticipating adverse effects and others expecting positive outcomes; however, little is known about the characteristics of people who are most likely to be interested in direct-to-consumer genetic testing. To that end, this study examines the association of individual dispositional differences with health risk perceptions and online information seeking related to a free genetic susceptibility test. Healthy adults enrolled in a large health maintenance organization were surveyed by telephone. Eligible participants (N = 1,959) were given access to a secure website that provided risk and benefit information about a genetic susceptibility test and given the option to be tested. Neuroticism was associated with increased perceptions of disease risk but not with logging on. Those scoring high in conscientiousness were more likely to log on. We found no evidence that neuroticism, a dispositional characteristic commonly linked to adverse emotional response, was predictive of online genetic information seeking in this sample of healthy adults.

  11. Current ethical and legal issues in health-related direct-to-consumer genetic testing.

    Science.gov (United States)

    Niemiec, Emilia; Kalokairinou, Louiza; Howard, Heidi Carmen

    2017-09-01

    A variety of health-related genetic testing is currently advertized directly to consumers. This article provides a timely overview of direct-to-consumer genetic testing (DTC GT) and salient ethical issues, as well as an analysis of the impact of the recently adopted regulation on in vitro diagnostic medical devices on DTC GT. DTC GT companies currently employ new testing approaches, report on a wide spectrum of conditions and target new groups of consumers. Such activities raise ethical issues including the questionable analytic and clinical validity of tests, the adequacy of informed consent, potentially misleading advertizing, testing in children, research uses and commercialization of genomic data. The recently adopted regulation on in vitro diagnostic medical devices may limit the offers of predisposition DTC GT in the EU market.

  12. [Direct-to-consumer genetic testing through Internet: marketing, ethical and social issues].

    Science.gov (United States)

    Ducournau, Pascal; Gourraud, Pierre-Antoine; Rial-Sebbag, Emmanuelle; Bulle, Alexandre; Cambon-Thomsen, Anne

    2011-01-01

    We probably did not anticipate all the consequences of the direct to consumer genetic tests on Internet, resulting from the combined skills of communication and genomic advances. What are the commercial strategies used by the companies offering direct-to-consumer genetic tests on Internet and what are the different social expectations on which they focus? Through a quantitative and qualitative analysis of the web sites offering such tests, it seems that these companies target a triple market based on: the "healthism" which raises health and hygiene to the top of the social values; the contemporary demands of the users to become actual actors of health decisions; and finally on the need for bio-social relationships. These three commercial strategies underlie various ethical and societal issues justifying a general analysis.

  13. Prostate Cancer Epigenetics: A Review on Gene Regulation

    Directory of Open Access Journals (Sweden)

    Lena Diaw

    2007-01-01

    Full Text Available Prostate cancer is the most common cancer in men in western countries, and its incidence is increasing steadily worldwide. Molecular changes including both genetic and epigenetic events underlying the development and progression of this disease are still not well understood. Epigenetic events are involved in gene regulation and occur through different mechanisms such as DNA methylation and histone modifi cations. Both DNA methylation and histone modifi cations affect gene regulation and play important roles either independently or by interaction in tumor initiation and progression. This review will discuss the genes associated with epigenetic alterations in prostate cancer progression: their regulation and importance as possible markers for the disease.

  14. Effect of Cryopreservation and Post-Cryopreservation Somatic Embryogenesis on the Epigenetic Fidelity of Cocoa (Theobroma cacao L.).

    Science.gov (United States)

    Adu-Gyamfi, Raphael; Wetten, Andy; Marcelino Rodríguez López, Carlos

    2016-01-01

    While cocoa plants regenerated from cryopreserved somatic embryos can demonstrate high levels of phenotypic variability, little is known about the sources of the observed variability. Previous studies have shown that the encapsulation-dehydration cryopreservation methodology imposes no significant extra mutational load since embryos carrying high levels of genetic variability are selected against during protracted culture. Also, the use of secondary rather than primary somatic embryos has been shown to further reduce the incidence of genetic somaclonal variation. Here, the effect of in vitro conservation, cryopreservation and post-cryopreservation generation of somatic embryos on the appearance of epigenetic somaclonal variation were comparatively assessed. To achieve this we compared the epigenetic profiles, generated using Methylation Sensitive Amplified Polymorphisms, of leaves collected from the ortet tree and from cocoa somatic embryos derived from three in vitro conditions: somatic embryos, somatic embryos cryopreserved in liquid nitrogen and somatic embryos generated from cryoproserved somatic embryos. Somatic embryos accumulated epigenetic changes but these were less extensive than in those regenerated after storage in LN. Furthermore, the passage of cryopreserved embryos through another embryogenic stage led to further increase in variation. Interestingly, this detected variability appears to be in some measure reversible. The outcome of this study indicates that the cryopreservation induced phenotypic variability could be, at least partially, due to DNA methylation changes. Phenotypic variability observed in cryostored cocoa somatic-embryos is epigenetic in nature. This variability is partially reversible, not stochastic in nature but a directed response to the in-vitro culture and cryopreservation.

  15. Elusive inheritance: Transgenerational effects and epigenetic inheritance in human environmental disease.

    Science.gov (United States)

    Martos, Suzanne N; Tang, Wan-Yee; Wang, Zhibin

    2015-07-01

    Epigenetic mechanisms involving DNA methylation, histone modification, histone variants and nucleosome positioning, and noncoding RNAs regulate cell-, tissue-, and developmental stage-specific gene expression by influencing chromatin structure and modulating interactions between proteins and DNA. Epigenetic marks are mitotically inherited in somatic cells and may be altered in response to internal and external stimuli. The idea that environment-induced epigenetic changes in mammals could be inherited through the germline, independent of genetic mechanisms, has stimulated much debate. Many experimental models have been designed to interrogate the possibility of transgenerational epigenetic inheritance and provide insight into how environmental exposures influence phenotypes over multiple generations in the absence of any apparent genetic mutation. Unexpected molecular evidence has forced us to reevaluate not only our understanding of the plasticity and heritability of epigenetic factors, but of the stability of the genome as well. Recent reviews have described the difference between transgenerational and intergenerational effects; the two major epigenetic reprogramming events in the mammalian lifecycle; these two events making transgenerational epigenetic inheritance of environment-induced perturbations rare, if at all possible, in mammals; and mechanisms of transgenerational epigenetic inheritance in non-mammalian eukaryotic organisms. This paper briefly introduces these topics and mainly focuses on (1) transgenerational phenotypes and epigenetic effects in mammals, (2) environment-induced intergenerational epigenetic effects, and (3) the inherent difficulties in establishing a role for epigenetic inheritance in human environmental disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Role of epigenetics in developmental biology and transgenerational inheritance.

    Science.gov (United States)

    Skinner, Michael K

    2011-03-01

    The molecular mechanisms involved in developmental biology and cellular differentiation have traditionally been considered to be primarily genetic. Environmental factors that influence early life critical windows of development generally do not have the capacity to modify genome sequence, nor promote permanent genetic modifications. Epigenetics provides a molecular mechanism for environment to influence development, program cellular differentiation, and alter the genetic regulation of development. The current review discusses how epigenetics can cooperate with genetics to regulate development and allow for greater plasticity in response to environmental influences. This impacts area such as cellular differentiation, tissue development, environmental induced disease etiology, epigenetic transgenerational inheritance, and the general systems biology of organisms and evolution. Copyright © 2011 Wiley-Liss, Inc.

  17. Epigenetic signature of birth weight discordance in adult twins

    DEFF Research Database (Denmark)

    Tan, Qihua; Nielsen, Morten Frost Munk; Heijmans, Bastiaan T

    2014-01-01

    between birth weight and adult life health while controlling for not only genetics but also postnatal rearing environment. We performed an epigenome-wide profiling on blood samples from 150 pairs of adult monozygotic twins discordant for birth weight to look for molecular evidence of epigenetic signatures...... profiling did not reveal epigenetic signatures of birth weight discordance although some sites displayed age-dependent intra-pair differential methylation in the extremely discordant twin pairs....

  18. Prostate Cancer Epigenetics: A Review on Gene Regulation

    OpenAIRE

    Diaw, Lena; Woodson, Karen; Gillespie, John W.

    2007-01-01

    Prostate cancer is the most common cancer in men in western countries, and its incidence is increasing steadily worldwide. Molecular changes including both genetic and epigenetic events underlying the development and progression of this disease are still not well understood. Epigenetic events are involved in gene regulation and occur through different mechanisms such as DNA methylation and histone modifi cations. Both DNA methylation and histone modifi cations affect gene regulation and play ...

  19. Epigenetic modification and inheritance in sexual reversal of fish

    OpenAIRE

    Shao, Changwei; Li, Qiye; Chen, Songlin; Zhang, Pei; Lian, Jinmin; Hu, Qiaomu; Sun, Bing; Jin, Lijun; Liu, Shanshan; Wang, Zongji; Zhao, Hongmei; Jin, Zonghui; Liang, Zhuo; Li, Yangzhen; Zheng, Qiumei

    2014-01-01

    Environmental sex determination (ESD) occurs in divergent, phylogenetically unrelated taxa, and in some species, co-occurs with genetic sex determination (GSD) mechanisms. Although epigenetic regulation in response to environmental effects has long been proposed to be associated with ESD, a systemic analysis on epigenetic regulation of ESD is still lacking. Using half-smooth tongue sole (Cynoglossus semilaevis) as a model—a marine fish that has both ZW chromosomal GSD and temperature-dependen...

  20. Epigenetics and Vasculitis: a Comprehensive Review.

    Science.gov (United States)

    Renauer, Paul; Coit, Patrick; Sawalha, Amr H

    2016-06-01

    Vasculitides represent a group of relatively rare systemic inflammatory diseases of the blood vessels. Despite recent progress in understanding the genetic basis and the underlying pathogenic mechanisms in vasculitis, the etiology and pathogenesis of vasculitis remain incompletely understood. Epigenetic dysregulation plays an important role in immune-mediated diseases, and the contribution of epigenetic aberrancies in vasculitis is increasingly being recognized. Histone modifications in the PR3 and MPO gene loci might be mechanistically involved in the pathogenesis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Similarly, other studies revealed important epigenetic contribution to other vasculitides, including Kawasaki disease and IgA vasculitis. More recently, genome-wide epigenomic studies have been performed in several vasculitides. A recent genome-wide DNA methylation study uncovered an important role for epigenetic remodeling of cytoskeleton-related genes in the pathogenesis of Behçet's disease and suggested that reversal of some of these DNA methylation changes associates with disease remission. Genome-wide DNA methylation profiling characterized the inflammatory response in temporal artery tissue from patients with giant cell arteritis and showed increased activation of calcineurin/nuclear factor of activated T cells (NFAT) signaling, prompting the suggestion that a specific calcineurin/NFAT inhibitor that is well tolerated and with the added beneficial anti-platelet activity, such as dipyridamole, might be of therapeutic potential in giant cell arteritis. While epigenetic studies in systemic vasculitis are still in their infancy, currently available data clearly indicate that investigating the epigenetic mechanisms underlying these diseases will help to better understand the pathogenesis of vasculitis and provide novel targets for the development of disease biomarkers and new therapies.

  1. Dynamic epigenetic states of maize centromeres

    Directory of Open Access Journals (Sweden)

    Yalin eLiu

    2015-10-01

    Full Text Available The centromere is a specialized chromosomal region identified as the major constriction, upon which the kinetochore complex is formed, ensuring accurate chromosome orientation and segregation during cell division. The rapid evolution of centromere DNA sequence and the conserved centromere function are two contradictory aspects of centromere biology. Indeed, the sole presence of genetic sequence is not sufficient for centromere formation. Various dicentric chromosomes with one inactive centromere have been recognized. It has also been found that de novo centromere formation is common on fragments in which centromeric DNA sequences are lost. Epigenetic factors play important roles in centromeric chromatin assembly and maintenance. Nondisjunction of the supernumerary B chromosome early prophase of meiosis I requires an active centromere. This review discusses recent studies in maize about genetic and epigenetic elements regulating formation and maintenance of centromere chromatin, as well as centromere behavior in meiosis.

  2. Epigenetic Modifications of Major Depressive Disorder

    Directory of Open Access Journals (Sweden)

    Kathleen Saavedra

    2016-08-01

    Full Text Available Major depressive disorder (MDD is a chronic disease whose neurological basis and pathophysiology remain poorly understood. Initially, it was proposed that genetic variations were responsible for the development of this disease. Nevertheless, several studies within the last decade have provided evidence suggesting that environmental factors play an important role in MDD pathophysiology. Alterations in epigenetics mechanism, such as DNA methylation, histone modification and microRNA expression could favor MDD advance in response to stressful experiences and environmental factors. The aim of this review is to describe genetic alterations, and particularly altered epigenetic mechanisms, that could be determinants for MDD progress, and how these alterations may arise as useful screening, diagnosis and treatment monitoring biomarkers of depressive disorders.

  3. The physics of epigenetics

    Science.gov (United States)

    Cortini, Ruggero; Barbi, Maria; Caré, Bertrand R.; Lavelle, Christophe; Lesne, Annick; Mozziconacci, Julien; Victor, Jean-Marc

    2016-04-01

    In higher organisms, all cells share the same genome, but every cell expresses only a limited and specific set of genes that defines the cell type. During cell division, not only the genome, but also the cell type is inherited by the daughter cells. This intriguing phenomenon is achieved by a variety of processes that have been collectively termed epigenetics: the stable and inheritable changes in gene expression patterns. This article reviews the extremely rich and exquisitely multiscale physical mechanisms that govern the biological processes behind the initiation, spreading, and inheritance of epigenetic states. These include not only the changes in the molecular properties associated with the chemical modifications of DNA and histone proteins, such as methylation and acetylation, but also less conventional changes, typically in the physics that governs the three-dimensional organization of the genome in cell nuclei. Strikingly, to achieve stability and heritability of epigenetic states, cells take advantage of many different physical principles, such as the universal behavior of polymers and copolymers, the general features of dynamical systems, and the electrostatic and mechanical properties related to chemical modifications of DNA and histones. By putting the complex biological literature in this new light, the emerging picture is that a limited set of general physical rules play a key role in initiating, shaping, and transmitting this crucial "epigenetic landscape." This new perspective not only allows one to rationalize the normal cellular functions, but also helps to understand the emergence of pathological states, in which the epigenetic landscape becomes dysfunctional.

  4. Direct-to-consumer genetic testing for predicting sports performance and talent identification: Consensus statement.

    Science.gov (United States)

    Webborn, Nick; Williams, Alun; McNamee, Mike; Bouchard, Claude; Pitsiladis, Yannis; Ahmetov, Ildus; Ashley, Euan; Byrne, Nuala; Camporesi, Silvia; Collins, Malcolm; Dijkstra, Paul; Eynon, Nir; Fuku, Noriyuki; Garton, Fleur C; Hoppe, Nils; Holm, Søren; Kaye, Jane; Klissouras, Vassilis; Lucia, Alejandro; Maase, Kamiel; Moran, Colin; North, Kathryn N; Pigozzi, Fabio; Wang, Guan

    2015-12-01

    The general consensus among sport and exercise genetics researchers is that genetic tests have no role to play in talent identification or the individualised prescription of training to maximise performance. Despite the lack of evidence, recent years have witnessed the rise of an emerging market of direct-to-consumer marketing (DTC) tests that claim to be able to identify children's athletic talents. Targeted consumers include mainly coaches and parents. There is concern among the scientific community that the current level of knowledge is being misrepresented for commercial purposes. There remains a lack of universally accepted guidelines and legislation for DTC testing in relation to all forms of genetic testing and not just for talent identification. There is concern over the lack of clarity of information over which specific genes or variants are being tested and the almost universal lack of appropriate genetic counselling for the interpretation of the genetic data to consumers. Furthermore independent studies have identified issues relating to quality control by DTC laboratories with different results being reported from samples from the same individual. Consequently, in the current state of knowledge, no child or young athlete should be exposed to DTC genetic testing to define or alter training or for talent identification aimed at selecting gifted children or adolescents. Large scale collaborative projects, may help to develop a stronger scientific foundation on these issues in the future. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  5. Xenopatients 2.0: reprogramming the epigenetic landscapes of patient-derived cancer genomes.

    Science.gov (United States)

    Menendez, Javier A; Alarcón, Tomás; Corominas-Faja, Bruna; Cuyàs, Elisabet; López-Bonet, Eugeni; Martin, Angel G; Vellon, Luciano

    2014-01-01

    In the science-fiction thriller film Minority Report, a specialized police department called "PreCrime" apprehends criminals identified in advance based on foreknowledge provided by 3 genetically altered humans called "PreCogs". We propose that Yamanaka stem cell technology can be similarly used to (epi)genetically reprogram tumor cells obtained directly from cancer patients and create self-evolving personalized translational platforms to foresee the evolutionary trajectory of individual tumors. This strategy yields a large stem cell population and captures the cancer genome of an affected individual, i.e., the PreCog-induced pluripotent stem (iPS) cancer cells, which are immediately available for experimental manipulation, including pharmacological screening for personalized "stemotoxic" cancer drugs. The PreCog-iPS cancer cells will re-differentiate upon orthotopic injection into the corresponding target tissues of immunodeficient mice (i.e., the PreCrime-iPS mouse avatars), and this in vivo model will run through specific cancer stages to directly explore their biological properties for drug screening, diagnosis, and personalized treatment in individual patients. The PreCog/PreCrime-iPS approach can perform sets of comparisons to directly observe changes in the cancer-iPS cell line vs. a normal iPS cell line derived from the same human genetic background. Genome editing of PreCog-iPS cells could create translational platforms to directly investigate the link between genomic expression changes and cellular malignization that is largely free from genetic and epigenetic noise and provide proof-of-principle evidence for cutting-edge "chromosome therapies" aimed against cancer aneuploidy. We might infer the epigenetic marks that correct the tumorigenic nature of the reprogrammed cancer cell population and normalize the malignant phenotype in vivo. Genetically engineered models of conditionally reprogrammable mice to transiently express the Yamanaka stemness factors

  6. Computer-Aided Drug Design in Epigenetics

    Directory of Open Access Journals (Sweden)

    Wenchao Lu

    2018-03-01

    Full Text Available Epigenetic dysfunction has been widely implicated in several diseases especially cancers thus highlights the therapeutic potential for chemical interventions in this field. With rapid development of computational methodologies and high-performance computational resources, computer-aided drug design has emerged as a promising strategy to speed up epigenetic drug discovery. Herein, we make a brief overview of major computational methods reported in the literature including druggability prediction, virtual screening, homology modeling, scaffold hopping, pharmacophore modeling, molecular dynamics simulations, quantum chemistry calculation, and 3D quantitative structure activity relationship that have been successfully applied in the design and discovery of epi-drugs and epi-probes. Finally, we discuss about major limitations of current virtual drug design strategies in epigenetics drug discovery and future directions in this field.

  7. Computer-Aided Drug Design in Epigenetics

    Science.gov (United States)

    Lu, Wenchao; Zhang, Rukang; Jiang, Hao; Zhang, Huimin; Luo, Cheng

    2018-01-01

    Epigenetic dysfunction has been widely implicated in several diseases especially cancers thus highlights the therapeutic potential for chemical interventions in this field. With rapid development of computational methodologies and high-performance computational resources, computer-aided drug design has emerged as a promising strategy to speed up epigenetic drug discovery. Herein, we make a brief overview of major computational methods reported in the literature including druggability prediction, virtual screening, homology modeling, scaffold hopping, pharmacophore modeling, molecular dynamics simulations, quantum chemistry calculation, and 3D quantitative structure activity relationship that have been successfully applied in the design and discovery of epi-drugs and epi-probes. Finally, we discuss about major limitations of current virtual drug design strategies in epigenetics drug discovery and future directions in this field. PMID:29594101

  8. Computer-Aided Drug Design in Epigenetics

    Science.gov (United States)

    Lu, Wenchao; Zhang, Rukang; Jiang, Hao; Zhang, Huimin; Luo, Cheng

    2018-03-01

    Epigenetic dysfunction has been widely implicated in several diseases especially cancers thus highlights the therapeutic potential for chemical interventions in this field. With rapid development of computational methodologies and high-performance computational resources, computer-aided drug design has emerged as a promising strategy to speed up epigenetic drug discovery. Herein, we make a brief overview of major computational methods reported in the literature including druggability prediction, virtual screening, homology modeling, scaffold hopping, pharmacophore modeling, molecular dynamics simulations, quantum chemistry calculation and 3D quantitative structure activity relationship that have been successfully applied in the design and discovery of epi-drugs and epi-probes. Finally, we discuss about major limitations of current virtual drug design strategies in epigenetics drug discovery and future directions in this field.

  9. Epigenetics in comparative biology: why we should pay attention.

    Science.gov (United States)

    Burggren, Warren W; Crews, David

    2014-07-01

    The past decade has seen an explosion of articles in scientific journals involving non-genetic influences on phenotype through modulation of gene function without changes in gene sequence. The excitement in modern molecular biology surrounding the impact exerted by the environment on development of the phenotype is focused largely on mechanism and has not incorporated questions asked (and answers provided) by early philosophers, biologists, and psychologists. As such, this emergence of epigenetic studies is somewhat "old wine in new bottles" and represents a reformulation of the old debate of preformationism versus epigenesis-one resolved in the 1800s. Indeed, this tendency to always look forward, with minimal concern or regard of what has gone before, has led to the present situation in which "true" epigenetic studies are believed to consist of one of two schools. The first is primarily medically based and views epigenetic mechanisms as pathways for disease (e.g., "the epigenetics of cancer"). The second is primarily from the basic sciences, particularly molecular genetics, and regards epigenetics as a potentially important mechanism for organisms exposed to variable environments across multiple generations. There is, however, a third, and separate, school based on the historical literature and debates and regards epigenetics as more of a perspective than a phenomenon. Against this backdrop, comparative integrative biologists are particularly well-suited to understand epigenetic phenomena as a way for organisms to respond rapidly with modified phenotypes (relative to natural selection) to changes in the environment. Using evolutionary principles, it is also possible to interpret "sunsetting" of modified phenotypes when environmental conditions result in a disappearance of the epigenetic modification of gene regulation. Comparative integrative biologists also recognize epigenetics as a potentially confounding source of variation in their data. Epigenetic

  10. Epigenetic mechanisms in neurological disease.

    Science.gov (United States)

    Jakovcevski, Mira; Akbarian, Schahram

    2012-08-01

    The exploration of brain epigenomes, which consist of various types of DNA methylation and covalent histone modifications, is providing new and unprecedented insights into the mechanisms of neural development, neurological disease and aging. Traditionally, chromatin defects in the brain were considered static lesions of early development that occurred in the context of rare genetic syndromes, but it is now clear that mutations and maladaptations of the epigenetic machinery cover a much wider continuum that includes adult-onset neurodegenerative disease. Here, we describe how recent advances in neuroepigenetics have contributed to an improved mechanistic understanding of developmental and degenerative brain disorders, and we discuss how they could influence the development of future therapies for these conditions.

  11. Epigenetics and assisted reproductive technologies

    DEFF Research Database (Denmark)

    Pinborg, Anja; Loft, Anne; Romundstad, Liv Bente

    2016-01-01

    Epigenetic modification controls gene activity without changes in the DNA sequence. The genome undergoes several phases of epigenetic programming during gametogenesis and early embryo development coinciding with assisted reproductive technologies (ART) treatments. Imprinting disorders have been...

  12. Epigenetics and lifestyle.

    Science.gov (United States)

    Alegría-Torres, Jorge Alejandro; Baccarelli, Andrea; Bollati, Valentina

    2011-06-01

    The concept of 'lifestyle' includes different factors such as nutrition, behavior, stress, physical activity, working habits, smoking and alcohol consumption. Increasing evidence shows that environmental and lifestyle factors may influence epigenetic mechanisms, such as DNA methylation, histone acetylation and miRNA expression. It has been identified that several lifestyle factors such as diet, obesity, physical activity, tobacco smoking, alcohol consumption, environmental pollutants, psychological stress and working on night shifts might modify epigenetic patterns. Most of the studies conducted so far have been centered on DNA methylation, whereas only a few investigations have studied lifestyle factors in relation to histone modifications and miRNAs. This article reviews current evidence indicating that lifestyle factors might affect human health via epigenetic mechanisms.

  13. Anxiety and Epigenetics.

    Science.gov (United States)

    Bartlett, Andrew A; Singh, Rumani; Hunter, Richard G

    2017-01-01

    Anxiety disorders are highly prevalent psychiatric disorders often comorbid with depression and substance abuse. Twin studies have shown that anxiety disorders are moderately heritable. Yet, genome-wide association studies (GWASs) have failed to identify gene(s) significantly associated with diagnosis suggesting a strong role for environmental factors and the epigenome. A number of anxiety disorder subtypes are considered "stress related." A large focus of research has been on the epigenetic and anxiety-like behavioral consequences of stress. Animal models of anxiety-related disorders have provided strong evidence for the role of stress on the epigenetic control of the hypothalamic-pituitary-adrenal (HPA) axis and of stress-responsive brain regions. Neuroepigenetics may continue to explain individual variation in susceptibility to environmental perturbations and consequently anxious behavior. Behavioral and pharmacological interventions aimed at targeting epigenetic marks associated with anxiety may prove fruitful in developing treatments.

  14. Epigenetics in prostate cancer.

    Science.gov (United States)

    Albany, Costantine; Alva, Ajjai S; Aparicio, Ana M; Singal, Rakesh; Yellapragada, Sarvari; Sonpavde, Guru; Hahn, Noah M

    2011-01-01

    Prostate cancer (PC) is the most commonly diagnosed nonskin malignancy and the second most common cause of cancer death among men in the United States. Epigenetics is the study of heritable changes in gene expression caused by mechanisms other than changes in the underlying DNA sequences. Two common epigenetic mechanisms, DNA methylation and histone modification, have demonstrated critical roles in prostate cancer growth and metastasis. DNA hypermethylation of cytosine-guanine (CpG) rich sequence islands within gene promoter regions is widespread during neoplastic transformation of prostate cells, suggesting that treatment-induced restoration of a "normal" epigenome could be clinically beneficial. Histone modification leads to altered tumor gene function by changing chromosome structure and the level of gene transcription. The reversibility of epigenetic aberrations and restoration of tumor suppression gene function have made them attractive targets for prostate cancer treatment with modulators that demethylate DNA and inhibit histone deacetylases.

  15. Epigenetics in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Costantine Albany

    2011-01-01

    Full Text Available Prostate cancer (PC is the most commonly diagnosed nonskin malignancy and the second most common cause of cancer death among men in the United States. Epigenetics is the study of heritable changes in gene expression caused by mechanisms other than changes in the underlying DNA sequences. Two common epigenetic mechanisms, DNA methylation and histone modification, have demonstrated critical roles in prostate cancer growth and metastasis. DNA hypermethylation of cytosine-guanine (CpG rich sequence islands within gene promoter regions is widespread during neoplastic transformation of prostate cells, suggesting that treatment-induced restoration of a “normal” epigenome could be clinically beneficial. Histone modification leads to altered tumor gene function by changing chromosome structure and the level of gene transcription. The reversibility of epigenetic aberrations and restoration of tumor suppression gene function have made them attractive targets for prostate cancer treatment with modulators that demethylate DNA and inhibit histone deacetylases.

  16. Epigenetics and cerebral organoids

    DEFF Research Database (Denmark)

    Forsberg, Sheena Louise; Ilieva, Mirolyuba; Maria Michel, Tanja

    2018-01-01

    also play a role. Some studies indicate a set of candidate genes with different DNA methylation profiles in ASD compared to healthy individuals. Thus epigenetic alterations could help bridging the gene-environment gap in deciphering the underlying neurobiology of autism. However, epigenome......-wide association studies (EWAS) have mainly included a very limited number of postmortem brain samples. Hence, cellular models mimicking brain development in vitro will be of great importance to study the critical epigenetic alterations and when they might happen. This review will give an overview of the state...... of the art concerning knowledge on epigenetic changes in autism and how new, cutting edge expertise based on three-dimensional (3D) stem cell technology models (brain organoids) can contribute in elucidating the multiple aspects of disease mechanisms....

  17. Health-related direct-to-consumer genetic testing: a review of companies' policies with regard to genetic testing in minors.

    Science.gov (United States)

    Borry, Pascal; Howard, Heidi C; Sénécal, Karine; Avard, Denise

    2010-03-01

    More and more companies are advertising and selling genetic tests directly to consumers. Considering the ethical, legal, and psychological concerns surrounding genetic testing in minors, a study of companies' websites was performed in order to describe and analyze their policies with respect to this issue. Of the 29 companies analyzed, 13 did not provide any information about this matter, eight companies allowed genetic testing upon parental request, four companies stated that their website is not directed to children under 18 years, and four companies suggested that in order to be tested, applicants should have reached the age of legal majority. If private companies offer genetic tests which are also offered in a clinical setting, can they be expected to adhere to the existing clinical guidelines with regard to these tests? If so, a certain ambiguity exists. Many companies are emphasizing in their disclaimers that their services are not medical services and should not be used as a basis for making medical decisions. Nonetheless, it remains debatable whether genetic testing in minors would be appropriate in this context. In line with the Advisory Committee on Genetic Testing, the Human Genetics Commission addressed the problem of non-consensual testing and recommended not to supply genetic testing services directly to those under the age of 16 or to those not able to make a competent decision regarding testing.

  18. Genetics and sport performance: current challenges and directions to the future

    Directory of Open Access Journals (Sweden)

    João Paulo Limongi França GUILHERME

    2014-03-01

    Full Text Available In recent years there has been a great progress in molecular biology techniques, which has facilitated the researches on influence of genetics on human performance. There are specific regions of DNA that can vary between individuals. Such variations (i.e., polymorphisms may, in part, explain why some individuals have differentiated responses to certain stimuli, including the responses to sports training. In a particular sport, the presence of specific polymorphisms may contribute to high levels of performance. Since 1998, several polymorphisms have been associated with athletic phenotypes; however the accumulation of information generated over these 15 years shows that the influence of genetics to sport is extremely complex. In this review, we will summarise the current status of the field, discussing the implications of available knowledge for the practice of professionals involved with the sport and suggesting future directions for research. We also discuss topics related to the importance of polygenic profile characterization of athletes, methods for the identification of new polymorphisms associated with physical performance, the use of genetic testing for predicting competitive success, and how crucial is the genetic profile for the success athletes in competition.

  19. Closure of population biobanks and direct-to-consumer genetic testing companies.

    Science.gov (United States)

    Zawati, Ma'n H; Borry, Pascal; Howard, Heidi Carmen

    2011-09-01

    Genetic research gained new momentum with the completion of the Human Genome Project in 2003. Formerly centered on the investigation of single-gene disorders, genetic research is increasingly targeting common complex diseases and in doing so is studying the whole genome, the environment and its impact on genomic variation. Consequently, biobanking initiatives have emerged around the world as a tool to sustain such progress. Whether they are small scale or longitudinal, public or private, commercial or non-commercial, biobanks should consider the possibility of closure. Interestingly, while raising important ethical issues, this topic has hardly been explored in the literature. Indeed, ethical issues associated with sale, insolvency, end of funding, or transfer of materials to other entities (which are all issues either related to or possible consequences of closure) are seldom the subject of discussion. In an attempt to fill this gap, this paper will discuss-using population and direct-to-consumer (DTC) genetic testing companies' biobanks as case studies-(1) international and national normative documents addressing the issue of closure and (2) the internal policies of population biobanks and DTC genetic testing companies. The analysis will inform the debate on biobank closure and elucidate the underlying ethical issues, which include, but are not limited to informed consent, storage and privacy.

  20. Socioeconomic influences on the effects of a genetic testing direct-to-consumer marketing campaign.

    Science.gov (United States)

    Bowen, D J; Harris, J; Jorgensen, C M; Myers, M F; Kuniyuki, A

    2010-01-01

    Direct-to-consumer marketing of genetic tests is beginning to appear in select markets, and little independent evaluation has been conducted on the effects of this marketing on consumer attitudes or behavior. The purpose of this paper is to identify the effects of socioeconomic status on women's reactions to such a campaign, including knowledge of the test, perceptions of personal risk, communications with others about the test, and interest in pursuing the test. The only United States provider of genetic testing for breast and ovarian cancer susceptibility (BRCA1/2 testing) conducted a pilot marketing campaign that targeted women aged 25-54 and their health care providers in 2 cities, Atlanta, Ga., and Denver, Colo. The design for the evaluation was a post campaign consumer survey, based on a cross-sectional stratified random sample of women in the 2 intervention sites and 2 comparison sites. The campaign had no differential impact by socioeconomic status. However, there was a consistent relationship between socioeconomic status and several outcome variables, including knowledge of the test, beliefs about the test, and desire to know about genetic risk. These data indicate that socioeconomic status may play a role in uptake of genetic services, regardless of response to a media campaign. Copyright 2009 S. Karger AG, Basel.

  1. Limits to behavioral evolution: the quantitative genetics of a complex trait under directional selection.

    Science.gov (United States)

    Careau, Vincent; Wolak, Matthew E; Carter, Patrick A; Garland, Theodore

    2013-11-01

    Replicated selection experiments provide a powerful way to study how "multiple adaptive solutions" may lead to differences in the quantitative-genetic architecture of selected traits and whether this may translate into differences in the timing at which evolutionary limits are reached. We analyze data from 31 generations (n=17,988) of selection on voluntary wheel running in house mice. The rate of initial response, timing of selection limit, and height of the plateau varied significantly between sexes and among the four selected lines. Analyses of litter size and realized selection differentials seem to rule out counterposing natural selection as a cause of the selection limits. Animal-model analyses showed that although the additive genetic variance was significantly lower in selected than control lines, both before and after the limits, the decrease was not sufficient to explain the limits. Moreover, directional selection promoted a negative covariance between additive and maternal genetic variance over the first 10 generations. These results stress the importance of replication in selection studies of higher-level traits and highlight the fact that long-term predictions of response to selection are not necessarily expected to be linear because of the variable effects of selection on additive genetic variance and maternal effects. © 2013 The Author(s). Evolution © 2013 The Society for the Study of Evolution.

  2. Regulation of drug metabolism and toxicity by multiple factors of genetics, epigenetics, lncRNAs, gut microbiota, and diseases: a meeting report of the 21st International Symposium on Microsomes and Drug Oxidations (MDO

    Directory of Open Access Journals (Sweden)

    Ai-Ming Yu

    2017-03-01

    Full Text Available Variations in drug metabolism may alter drug efficacy and cause toxicity; better understanding of the mechanisms and risks shall help to practice precision medicine. At the 21st International Symposium on Microsomes and Drug Oxidations held in Davis, California, USA, in October 2–6, 2016, a number of speakers reported some new findings and ongoing studies on the regulation mechanisms behind variable drug metabolism and toxicity, and discussed potential implications to personalized medications. A considerably insightful overview was provided on genetic and epigenetic regulation of gene expression involved in drug absorption, distribution, metabolism, and excretion (ADME and drug response. Altered drug metabolism and disposition as well as molecular mechanisms among diseased and special populations were presented. In addition, the roles of gut microbiota in drug metabolism and toxicology as well as long non-coding RNAs in liver functions and diseases were discussed. These findings may offer new insights into improved understanding of ADME regulatory mechanisms and advance drug metabolism research.

  3. Prediction of direct and indirect genetic gains and genotypic correlations in rubber tree progenies

    Directory of Open Access Journals (Sweden)

    Cecília Khusala Verardi

    2011-09-01

    Full Text Available The objective of this work was to estimate the genetic parameters, genotypic and phenotypic correlations, and direct and indirect genetic gains among and within rubber tree (Hevea brasiliensis progenies. The experiment was set up at the Municipality of Jaú, SP, Brazil. A randomized complete block design was used, with 22 treatments (progenies, 6 replicates, and 10 plants per plot at a spacing of 3x3 m. Three‑year‑old progenies were assessed for girth, rubber yield, and bark thickness by direct and indirect gains and genotypic correlations. The number of latex vessel rings showed the best correlations, correlating positively and significantly with girth and bark thickness. Selection gains among progenies were greater than within progeny for all the variables analyzed. Total gains obtained were high, especially for girth increase and rubber yield, which were 93.38 and 105.95%, respectively. Young progeny selection can maximize the expected genetic gains, reducing the rubber tree selection cycle.

  4. Epigenetic Therapy in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Stephen V Liu

    2013-05-01

    Full Text Available Epigenetic dysregulation of gene function has been strongly implicated in carcinogenesis and is one of the mechanisms contributing to the development of lung cancer. The inherent reversibility of epigenetic alterations makes them viable therapeutic targets. Here, we review the therapeutic implications of epigenetic changes in lung cancer, and recent advances in therapeutic strategies targeting DNA methylation and histone acetylation.

  5. Epigenetic Risk Factors in PTSD and Depression

    Directory of Open Access Journals (Sweden)

    Florian Joachim Raabe

    2013-08-01

    Full Text Available Epidemiological and clinical studies have shown that children exposed to adverse experiences are at increased risk for the development of depression, anxiety disorders and PTSD. A history of child abuse and maltreatment increases the likelihood of being subsequently exposed to traumatic events or of developing PTSD as an adult. The brain is highly plastic during early life and encodes acquired information into lasting memories that normally subserve adaptation. Translational studies in rodents showed that enduring sensitization of neuronal and neuroendocrine circuits in response to early life adversity are likely risk factors of life time vulnerability to stress. Hereby, the hypothalamic-pituitary-adrenal (HPA axis integrates cognitive, behavioural and emotional responses to early-life stress and can be epigenetically programmed during sensitive windows of development. Epigenetic mechanisms, comprising reciprocal regulation of chromatin structure and DNA methylation, are important to establish and maintain sustained, yet potentially reversible, changes in gene transcription. The relevance of these findings for the development of PTSD requires further studies in humans where experience-dependent epigenetic programming can additionally depend on genetic variation in the underlying substrates which may protect from or advance disease development. Overall, identification of early-life stress associated epigenetic risk markers informing on previous stress history can help to advance early diagnosis, personalized prevention and timely therapeutic interventions, thus reducing long-term social and health costs.

  6. Internet-Based Direct-to-Consumer Genetic Testing: A Systematic Review.

    Science.gov (United States)

    Covolo, Loredana; Rubinelli, Sara; Ceretti, Elisabetta; Gelatti, Umberto

    2015-12-14

    Direct-to-consumer genetic tests (DTC-GT) are easily purchased through the Internet, independent of a physician referral or approval for testing, allowing the retrieval of genetic information outside the clinical context. There is a broad debate about the testing validity, their impact on individuals, and what people know and perceive about them. The aim of this review was to collect evidence on DTC-GT from a comprehensive perspective that unravels the complexity of the phenomenon. A systematic search was carried out through PubMed, Web of Knowledge, and Embase, in addition to Google Scholar according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist with the key term "Direct-to-consumer genetic test." In the final sample, 118 articles were identified. Articles were summarized in five categories according to their focus on (1) knowledge of, attitude toward use of, and perception of DTC-GT (n=37), (2) the impact of genetic risk information on users (n=37), (3) the opinion of health professionals (n=20), (4) the content of websites selling DTC-GT (n=16), and (5) the scientific evidence and clinical utility of the tests (n=14). Most of the articles analyzed the attitude, knowledge, and perception of DTC-GT, highlighting an interest in using DTC-GT, along with the need for a health care professional to help interpret the results. The articles investigating the content analysis of the websites selling these tests are in agreement that the information provided by the companies about genetic testing is not completely comprehensive for the consumer. Given that risk information can modify consumers' health behavior, there are surprisingly few studies carried out on actual consumers and they do not confirm the overall concerns on the possible impact of DTC-GT. Data from studies that investigate the quality of the tests offered confirm that they are not informative, have little predictive power, and do not measure genetic risk

  7. Internet-Based Direct-to-Consumer Genetic Testing: A Systematic Review

    Science.gov (United States)

    Rubinelli, Sara; Ceretti, Elisabetta; Gelatti, Umberto

    2015-01-01

    Background Direct-to-consumer genetic tests (DTC-GT) are easily purchased through the Internet, independent of a physician referral or approval for testing, allowing the retrieval of genetic information outside the clinical context. There is a broad debate about the testing validity, their impact on individuals, and what people know and perceive about them. Objective The aim of this review was to collect evidence on DTC-GT from a comprehensive perspective that unravels the complexity of the phenomenon. Methods A systematic search was carried out through PubMed, Web of Knowledge, and Embase, in addition to Google Scholar according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist with the key term “Direct-to-consumer genetic test.” Results In the final sample, 118 articles were identified. Articles were summarized in five categories according to their focus on (1) knowledge of, attitude toward use of, and perception of DTC-GT (n=37), (2) the impact of genetic risk information on users (n=37), (3) the opinion of health professionals (n=20), (4) the content of websites selling DTC-GT (n=16), and (5) the scientific evidence and clinical utility of the tests (n=14). Most of the articles analyzed the attitude, knowledge, and perception of DTC-GT, highlighting an interest in using DTC-GT, along with the need for a health care professional to help interpret the results. The articles investigating the content analysis of the websites selling these tests are in agreement that the information provided by the companies about genetic testing is not completely comprehensive for the consumer. Given that risk information can modify consumers’ health behavior, there are surprisingly few studies carried out on actual consumers and they do not confirm the overall concerns on the possible impact of DTC-GT. Data from studies that investigate the quality of the tests offered confirm that they are not informative, have little predictive

  8. Recent developments in epigenetics of acute and chronic kidney diseases.

    Science.gov (United States)

    Reddy, Marpadga A; Natarajan, Rama

    2015-08-01

    The growing epidemic of obesity and diabetes, the aging population as well as prevalence of drug abuse has led to significant increases in the rates of the closely associated acute and chronic kidney diseases, including diabetic nephropathy. Furthermore, evidence shows that parental behavior and diet can affect the phenotype of subsequent generations via epigenetic transmission mechanisms. These data suggest a strong influence of the environment on disease susceptibility and that, apart from genetic susceptibility, epigenetic mechanisms need to be evaluated to gain critical new information about kidney diseases. Epigenetics is the study of processes that control gene expression and phenotype without alterations in the underlying DNA sequence. Epigenetic modifications, including cytosine DNA methylation and covalent post-translational modifications of histones in chromatin, are part of the epigenome, the interface between the stable genome and the variable environment. This dynamic epigenetic layer responds to external environmental cues to influence the expression of genes associated with disease states. The field of epigenetics has seen remarkable growth in the past few years with significant advances in basic biology, contributions to human disease, as well as epigenomics technologies. Further understanding of how the renal cell epigenome is altered by metabolic and other stimuli can yield novel new insights into the pathogenesis of kidney diseases. In this review, we have discussed the current knowledge on the role of epigenetic mechanisms (primarily DNAme and histone modifications) in acute and chronic kidney diseases, and their translational potential to identify much needed new therapies.

  9. Mapping the Technological Knowledge Landscape: The Case of Epigenetics.

    Science.gov (United States)

    Song, Chie Hoon; Yoon, Janghyeok; Ko, Namuk; Han, Jeung-Whan

    2016-01-01

    Epigenetics is a biomedical novelty in drug design and disease control whose mechanisms play a significant role in transferring environmental signals to determine patterns of gene expression. Systematic identification of the main trends in epigenetics patenting activity provides insights into fundamental building blocks of this research field and policy guidance to funding agencies. The review aims at providing a comprehensive overview of the research and development trend in epigenetics by mapping the knowledge structure in patent landscape. Citation-based patent network analysis was performed to visualize the technological landscape. We focus on identifying the structure of the knowledge networks to study the technological trajectories. Patents that play an integral part in the dissemination and bridging of the technical knowledge are located and ranked. The latent topics in patent documents are highlighted by means of a topic modeling technique. Visualization of the patent network results in four main clusters. The first two clusters deal with the inhibition of histone deacetylase (HDAC). The third cluster covers inventions related to DNA methylation, which represents an epigenetic signaling tool that cells use to control gene expression. The fourth cluster encompasses computing systems and data mining techniques for identifying combinations of genetic and epigenetic attributes related to health and lifestyle improvements. We are in the growth period of gathering knowledge on various mechanisms of epigenetic regulation. There is enormous potential for improving healthcare through better understanding of the interrelationships between epigenetic control of gene expression and compounds that trigger these modifications.

  10. Evolution, epigenetics and cooperation

    Indian Academy of Sciences (India)

    Explanations for biological evolution in terms of changes in gene frequencies refer to outcomes rather than process. Integrating epigenetic studies with older evolutionary theories has drawn attention to the ways in which evolution occurs. Adaptation at the level of the gene is givingway to adaptation at the level of the ...

  11. Epigenetic changes in myelofibrosis

    DEFF Research Database (Denmark)

    Nielsen, Helene Myrtue; Andersen, Christen Lykkegaard; Westman, Maj

    2017-01-01

    , in 'inflammatory disease' in MF mononuclear cells, and in 'immunological diseases' in MF granulocytes. Only few differentially methylated CpG sites were common among the three cell populations. Mutations in the epigenetic regulators ASXL1 (47%) and TET2 (20%) were not associated with a specific DNA methylation...

  12. The epigenetics of obesity

    Science.gov (United States)

    Maternal nutrition at the time of conception and during pregnancy is considered a factor for individual differences in having obesity. The mechanisms underlying this association are likely partially epigenetic in nature, but pinning down the exact nature, location, and timing of these changes remain...

  13. Comparison of a constraint directed search to a genetic algorithm in a scheduling application

    International Nuclear Information System (INIS)

    Abbott, L.

    1993-01-01

    Scheduling plutonium containers for blending is a time-intensive operation. Several constraints must be taken into account; including the number of containers in a dissolver run, the size of each dissolver run, and the size and target purity of the blended mixture formed from these runs. Two types of algorithms have been used to solve this problem: a constraint directed search and a genetic algorithm. This paper discusses the implementation of these two different approaches to the problem and the strengths and weaknesses of each algorithm

  14. Directional Migration in Esophageal Squamous Cell Carcinoma (ESCC) is Epigenetically Regulated by SET Nuclear Oncogene, a Member of the Inhibitor of Histone Acetyltransferase Complex

    OpenAIRE

    Xiang Yuan; Xinshuai Wang; Bianli Gu; Yingjian Ma; Yiwen Liu; Man Sun; Jinyu Kong; Wei Sun; Huizhi Wang; Fuyou Zhou; Shegan Gao

    2017-01-01

    Directional cell migration is of fundamental importance to a variety of biological events, including metastasis of malignant cells. Herein, we specifically investigated SET oncoprotein, a subunit of the recently identified inhibitor of acetyltransferases (INHAT) complex and identified its role in the establishment of front–rear cell polarity and directional migration in Esophageal Squamous Cell Carcinoma (ESCC). We further define the molecular circuits that govern these processes by showing t...

  15. Epigenetics and obesity: a relationship waiting to be explained.

    Science.gov (United States)

    Symonds, Michael E; Budge, Helen; Frazier-Wood, Alexis C

    2013-01-01

    Obesity can have multifactorial causes that may change with development and are not simply attributable to one's genetic constitution. To date, expensive and laborious genome-wide association studies have only ascribed a small contribution of genetic variants to obesity. The emergence of the field of epigenetics now offers a new paradigm with which to study excess fat mass. Currently, however, there are no compelling epigenetic studies to explain the role of epigenetics in obesity, especially from a developmental perspective. It is clear that until there are advances in the understanding of the main mechanisms by which different fat types, i.e. brown, beige, and white, are established and how these differ between depots and species, population-based studies designed to determine specific aspects of epigenetics will be potentially limited. Obesity is a slowly evolving condition that is not simply explained by changes in the intake of one macronutrient. The latest advances in epigenetics, coupled with the establishment of relevant longitudinal models of obesity, which incorporate functionally relevant end points, may now permit the precise contribution of epigenetic modifications to excess fat mass to be effectively studied. © 2013 S. Karger AG, Basel.

  16. Awareness and uptake of direct-to-consumer genetic testing among cancer cases, their relatives, and controls: the Northwest Cancer Genetics Network.

    Science.gov (United States)

    Hall, Taryn O; Renz, Anne D; Snapinn, Katherine W; Bowen, Deborah J; Edwards, Karen L

    2012-07-01

    To determine if awareness of, interest in, and use of direct-to-consumer (DTC) genetic testing is greater in a sample of high-risk individuals (cancer cases and their relatives), compared to controls. Participants were recruited from the Northwest Cancer Genetics Network. A follow-up survey was mailed to participants to assess DTC genetic testing awareness, interest, and use. One thousand two hundred sixty-seven participants responded to the survey. Forty-nine percent of respondents were aware of DTC genetic testing. Of those aware, 19% indicated interest in obtaining and testing. Additional information supplied by respondents who reported use of DTC genetic tests indicated that 55% of these respondents likely engaged in clinical genetic testing, rather than DTC genetic testing. Awareness of DTC genetic testing was greater in our sample of high-risk individuals than in controls and population-based studies. Although interest in and use of these tests among cases in our sample were equivalent to other population-based studies, interest in testing was higher among relatives and people who self-referred for a registry focused on cancer than among cases and controls. Additionally, our results suggest that there may be some confusion about what constitutes DTC genetic testing.

  17. Prenatal and early life influences on epigenetic age in children

    DEFF Research Database (Denmark)

    Simpkin, Andrew J; Hemani, Gibran; Suderman, Matthew

    2016-01-01

    age for these samples. AA was defined as the residuals from regressing epigenetic age on actual age. AA was tested for associations with cross-sectional clinical variables in children. We identified associations between AA and sex, birth weight, birth by caesarean section and several maternal......). In children, epigenetic AA measures are associated with several clinically relevant variables, and early life exposures appear to be associated with changes in AA during adolescence. Further research into epigenetic aging, including the use of causal inference methods, is required to better our understanding......DNA methylation-based biomarkers of aging are highly correlated with actual age. Departures of methylation-estimated age from actual age can be used to define epigenetic measures of child development or age acceleration (AA) in adults. Very little is known about genetic or environmental...

  18. Prostate Cancer: Epigenetic Alterations, Risk Factors, and Therapy

    Directory of Open Access Journals (Sweden)

    Mankgopo M. Kgatle

    2016-01-01

    Full Text Available Prostate cancer (PCa is the most prevalent urological cancer that affects aging men in South Africa, and mechanisms underlying prostate tumorigenesis remain elusive. Research advancements in the field of PCa and epigenetics have allowed for the identification of specific alterations that occur beyond genetics but are still critically important in the pathogenesis of tumorigenesis. Anomalous epigenetic changes associated with PCa include histone modifications, DNA methylation, and noncoding miRNA. These mechanisms regulate and silence hundreds of target genes including some which are key components of cellular signalling pathways that, when perturbed, promote tumorigenesis. Elucidation of mechanisms underlying epigenetic alterations and the manner in which these mechanisms interact in regulating gene transcription in PCa are an unmet necessity that may lead to novel chemotherapeutic approaches. This will, therefore, aid in developing combination therapies that will target multiple epigenetic pathways, which can be used in conjunction with the current conventional PCa treatment.

  19. Mitochondrial regulation of epigenetics and its role in human diseases

    DEFF Research Database (Denmark)

    Minocherhomji, Sheroy; Tollefsbol, Trygve O; Singh, Keshav K

    2012-01-01

    as the sole pathogenic factor suggesting that additional mechanisms contribute to lack of genotype and clinical phenotype correlationship. An increasing number of studies have identified a possible effect on the epigenetic landscape of the nuclear genome as a consequence of mitochondrial dysfunction....... In particular, these studies demonstrate reversible or irreversible changes in genomic DNA methylation profiles of the nuclear genome. Here we review how mitochondria damage checkpoint (mitocheckpoint) induces epigenetic changes in the nucleus. Persistent pathogenic mutations in mtDNA may also lead...... to epigenetic changes causing genomic instability in the nuclear genome. We propose that "mitocheckpoint" mediated epigenetic and genetic changes may play key roles in phenotypic variation related to mitochondrial diseases or host of human diseases in which mitochondrial defect plays a primary role....

  20. Epigenetic transmission of Holocaust trauma: can nightmares be inherited?

    Science.gov (United States)

    Kellermann, Natan Pf

    2013-01-01

    The Holocaust left its visible and invisible marks not only on the survivors, but also on their children. Instead of numbers tattooed on their forearms, however, they may have been marked epigenetically with a chemical coating upon their chromosomes, which would represent a kind of biological memory of what the parents experienced. as a result, some suffer from a general vulnerability to stress while others are more resilient. Previous research assumed that such transmission was caused by environmental factors, such as the parents' childrearing behavior. New research, however, indicates that these transgenerational effects may have been also (epi) genetically transmitted to their children. Integrating both hereditary and environmental factors, epigenetics adds a new and more comprehensive psychobiological dimension to the explanation of transgenerational transmission of trauma. Specifically, epigenetics may explain why latent transmission becomes manifest under stress. a general theoretical overview of epigenetics and its relevance to research on trauma transmission is presented.

  1. Characterisation of genetic markers in Mungbean using direct amplification of length polymorphisms (DALP)

    International Nuclear Information System (INIS)

    Kumar, S.V.; Tan, S.G.; Quah, S.C.

    2000-01-01

    A newly developed technique, Direct Amplification of Length Polymorphisms (DALP), developed by Desmarais and co-workers in 1998 was successfully used to identify and characterise new genetic markers in mungbean (Vigyia radiata). DALP uses an arbitrarily primed PCR (AP-PCR) to produce genomic fingerprints and is specifically designed to enable direct sequencing of polymorphic bands. In this study, an oligonucleotide pair DALP235 and DAPLR were tested on four varieties of mungbean (V3476, P4281, V5973 and V5784) and produced, through PCR, specific multibanded fingerprints which showed polymorphisms. These polymorphic bands are the result of length polymorphisms as well as absence and presence of bands. Some of the polymorphic zones may be codominantly inherited and may be potential microsatellites. The success of DALP in characterising new polymorphic loci and its ability to discover microsatellites without the use of priori knowledge of the mungbean genome is revolutionary. This would greatly facilitate the breeding and improvement of the crop. (author)

  2. Testing for direct genetic effects using a screening step in family-based association studies

    Directory of Open Access Journals (Sweden)

    Sharon M Lutz

    2013-11-01

    Full Text Available In genome wide association studies (GWAS, families based studies tend to have less power to detect genetic associations than population based studies, such as case-control studies. This can be an issue when testing if genes in a family based GWAS have a direct effect on the phenotype of interest or if the genes act indirectly through a secondary phenotype. When multiple SNPs are tested for a direct effect in the family based study, a screening step can be used to minimize the burden of multiple comparisons in the causal analysis. We propose a 2-stage screening step that can be incorporated into the family based association test (FBAT approach similar to the conditional mean model approach in the VanSteen-algorithm [1]. Simulations demonstrate that the type 1 error is preserved and this method is advantageous when multiple markers are tested. This method is illustrated by an application to the Framingham Heart Study.

  3. Traditional Amerindian cultivators combine directional and ideotypic selection for sustainable management of cassava genetic diversity.

    Science.gov (United States)

    Duputié, A; Massol, F; David, P; Haxaire, C; McKey, D

    2009-06-01

    Plant domestication provides striking examples of rapid evolution. Yet, it involves more complex processes than plain directional selection. Understanding the dynamics of diversity in traditional agroecosystems is both a fundamental goal in evolutionary biology and a practical goal in conservation. We studied how Amerindian cultivators maintain dynamically evolving gene pools in cassava. Farmers purposely maintain diversity in the form of phenotypically distinct, clonally propagated landraces. Landrace gene pools are continuously renewed by incorporating seedlings issued from spontaneous sexual reproduction. This poses two problems: agronomic quality may decrease because some seedlings are inbred, and landrace identity may be progressively lost through the incorporation of unrelated seedlings. Using a large microsatellite dataset, we show that farmers solve these problems by applying two kinds of selection: directional selection against inbred genotypes, and counter-selection of off-type phenotypes, which maintains high intra-landrace relatedness. Thus, cultural elements such as ideotypes (a representation of the ideal phenotype of a landrace) can shape genetic diversity.

  4. Genetic gatekeepers: regulating direct-to-consumer genomic services in an era of participatory medicine.

    Science.gov (United States)

    Palmer, Jessica Elizabeth

    2012-01-01

    Should consumers be able to obtain information about their own bodies, even if it has no proven medical value? Direct-to-consumer ("DTC") genomic companies offer consumers two services: generation of the consumer's personal genetic sequence, and interpretation of that sequence in light of current research. Concerned that consumers will misunderstand genomic information and make ill-advised health decisions, regulators, legislators and scholars have advocated restricted access to DTC genomic services. The Food and Drug Administration, which has historically refrained from regulating most genetic tests, has announced its intent to treat DTC genomic services as medical devices because they make "medical claims." This Article argues that FDA regulation of genomic services as medical devices would be counterproductive. Clinical laboratories conducting genetic tests are already overseen by a federal regime administered by the Centers for Medicare and Medicaid Services. While consumers and clinicians would benefit from clearer communication of test results and their health implications, FDA's gatekeeping framework is ill-suited to weigh the safety and efficacy of genomic information that is not medically actionable in traditional ways. Playing gatekeeper would burden FDA's resources, conflict with the patient-empowering policies promoted by personalized medicine initiatives, impair individuals' access to information in which they have powerful autonomy interests, weaken novel participatory research infrastructures, and set a poor precedent for the future regulation of medical information. Rather than applying its risk-based regulatory framework to genetic information, FDA should ameliorate regulatory uncertainty by working with the Federal Trade Commission and Centers for Medicare and Medicaid Services to ensure that DTC genomic services deliver analytically valid data, market and implement their services in a truthful manner, and fully disclose the limitations of their

  5. Transgenic Epigenetics: Using Transgenic Organisms to Examine Epigenetic Phenomena

    Directory of Open Access Journals (Sweden)

    Lori A. McEachern

    2012-01-01

    Full Text Available Non-model organisms are generally more difficult and/or time consuming to work with than model organisms. In addition, epigenetic analysis of model organisms is facilitated by well-established protocols, and commercially-available reagents and kits that may not be available for, or previously tested on, non-model organisms. Given the evolutionary conservation and widespread nature of many epigenetic mechanisms, a powerful method to analyze epigenetic phenomena from non-model organisms would be to use transgenic model organisms containing an epigenetic region of interest from the non-model. Interestingly, while transgenic Drosophila and mice have provided significant insight into the molecular mechanisms and evolutionary conservation of the epigenetic processes that target epigenetic control regions in other model organisms, this method has so far been under-exploited for non-model organism epigenetic analysis. This paper details several experiments that have examined the epigenetic processes of genomic imprinting and paramutation, by transferring an epigenetic control region from one model organism to another. These cross-species experiments demonstrate that valuable insight into both the molecular mechanisms and evolutionary conservation of epigenetic processes may be obtained via transgenic experiments, which can then be used to guide further investigations and experiments in the species of interest.

  6. Epigenetics in prostate cancer: biologic and clinical relevance.

    Science.gov (United States)

    Jerónimo, Carmen; Bastian, Patrick J; Bjartell, Anders; Carbone, Giuseppina M; Catto, James W F; Clark, Susan J; Henrique, Rui; Nelson, William G; Shariat, Shahrokh F

    2011-10-01

    Prostate cancer (PCa) is one of the most common human malignancies and arises through genetic and epigenetic alterations. Epigenetic modifications include DNA methylation, histone modifications, and microRNAs (miRNA) and produce heritable changes in gene expression without altering the DNA coding sequence. To review progress in the understanding of PCa epigenetics and to focus upon translational applications of this knowledge. PubMed was searched for publications regarding PCa and DNA methylation, histone modifications, and miRNAs. Reports were selected based on the detail of analysis, mechanistic support of data, novelty, and potential clinical applications. Aberrant DNA methylation (hypo- and hypermethylation) is the best-characterized alteration in PCa and leads to genomic instability and inappropriate gene expression. Global and locus-specific changes in chromatin remodeling are implicated in PCa, with evidence suggesting a causative dysfunction of histone-modifying enzymes. MicroRNA deregulation also contributes to prostate carcinogenesis, including interference with androgen receptor signaling and apoptosis. There are important connections between common genetic alterations (eg, E twenty-six fusion genes) and the altered epigenetic landscape. Owing to the ubiquitous nature of epigenetic alterations, they provide potential biomarkers for PCa detection, diagnosis, assessment of prognosis, and post-treatment surveillance. Altered epigenetic gene regulation is involved in the genesis and progression of PCa. Epigenetic alterations may provide valuable tools for the management of PCa patients and be targeted by pharmacologic compounds that reverse their nature. The potential for epigenetic changes in PCa requires further exploration and validation to enable translation to the clinic. Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  7. Epigenetics of psoriatic disease: A systematic review and critical appraisal.

    Science.gov (United States)

    Pollock, Remy A; Abji, Fatima; Gladman, Dafna D

    2017-03-01

    Psoriasis is an inflammatory disease of the skin that is sometimes accompanied by an auto-inflammatory arthritis called psoriatic arthritis (PsA). Psoriasis and PsA are multifactorial diseases that result from complex interactions of environmental and genetic risk factors. Epigenetic marks, which are labile chemical marks with diverse functions, form a layer of biological information that sits at the interface of genetics and the environment. Aberrant epigenetic regulation has been previously implicated in other rheumatological disorders. The purpose of this review is to summarize and critically evaluate the nascent literature on epigenetics in psoriasis and PsA. A systematic review yielded 52 primary articles after applying inclusion and exclusion criteria. Data were extracted using a standardized template and study quality assessed using a methodological quality checklist. Studies reflect a broad range of epigenetic sub-disciplines, the most common being DNA methylation, followed by the parent of origin effect or genomic imprinting, expression or activity of epigenetic modifying enzymes, and histone modifications. Epidemiological studies demonstrating excessive paternal transmission provided the earliest evidence of epigenetic deregulation in psoriatic disease, however few studies have examined its molecular mechanisms. Methylation studies evolved rapidly from low resolution global to targeted analyses of known psoriatic disease susceptibility loci such as HLA-C*0602. The recent explosion of epigenome-wide association studies has provided us with novel insights into psoriasis pathogenesis, and the mechanism of action of UVB, methotrexate, and anti-TNF therapies, as well as molecular signatures of psoriasis that may have clinical relevance. Finally, recent studies of pharmacological inhibitors of epigenetic modifier enzymes demonstrate their potential applicability as novel treatment modalities for psoriasis. Challenges of epigenetics research in psoriasis and Ps

  8. Direct to consumer genetic testing and the libertarian right to test.

    Science.gov (United States)

    Bonython, Wendy Elizabeth; Arnold, Bruce Baer

    2017-08-20

    Loi recently proposed a libertarian right to direct to consumer genetic testing (DTCGT)- independent of autonomy or utility-reflecting Cohen's work on self-ownership and Hohfeld's model of jural relations. Cohen's model of libertarianism dealt principally with self-ownership of the physical body. Although Loi adequately accounts for the physical properties of DNA, DNA is also an informational substrate, highly conserved within families. Information about the genome of relatives of the person undergoing testing may be extrapolated without requiring direct engagement with their personal physical copy of the genome, triggering rights and interests of relatives that may differ from the rights and interests of others, that is, individual consumers, testing providers and regulators. Loi argued that regulatory interference with exercise of the right required justification, whereas prima facie exercise of the right did not. Justification of regulatory interference could include 'conflict with other people's rights', 'aggressive' use of the genome and 'harming others'. Harms potentially experienced by relatives as a result of the individual's exercise of a right to test include breach of genetic privacy, violation of their right to determine when, and if, they undertake genetic testing and discrimination. Such harms may justify regulatory intervention, in the event they are recognised; motives driving 'aggressive' use of the genome may also be relevant. Each of the above criteria requires clarification, as potential redundancies and tensions exist between them, with different implications affecting different groups of rights holders. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  9. Pharmacogenetic testing through the direct-to-consumer genetic testing company 23andMe.

    Science.gov (United States)

    Lu, Mengfei; Lewis, Cathryn M; Traylor, Matthew

    2017-06-19

    Rapid advances in scientific research have led to an increase in public awareness of genetic testing and pharmacogenetics. Direct-to-consumer (DTC) genetic testing companies, such as 23andMe, allow consumers to access their genetic information directly through an online service without the involvement of healthcare professionals. Here, we evaluate the clinical relevance of pharmacogenetic tests reported by 23andMe in their UK tests. The research papers listed under each 23andMe report were evaluated, extracting information on effect size, sample size and ethnicity. A wider literature search was performed to provide a fuller assessment of the pharmacogenetic test and variants were matched to FDA recommendations. Additional evidence from CPIC guidelines, PharmGKB, and Dutch Pharmacogenetics Working Group was reviewed to determine current clinical practice. The value of the tests across ethnic groups was determined, including information on linkage disequilibrium between the tested SNP and causal pharmacogenetic variant, where relevant. 23andMe offers 12 pharmacogenetic tests to their UK customers, some of which are in standard clinical practice, and others which are less widely applied. The clinical validity and clinical utility varies extensively between tests. The variants tested are likely to have different degrees of sensitivity due to different risk allele frequencies and linkage disequilibrium patterns across populations. The clinical relevance depends on the ethnicity of the individual and variability of pharmacogenetic markers. Further research is required to determine causal variants and provide more complete assessment of drug response and side effects. 23andMe reports provide some useful pharmacogenetics information, mirroring clinical tests that are in standard use. Other tests are unspecific, providing limited guidance and may not be useful for patients without professional interpretation. Nevertheless, DTC companies like 23andMe act as a powerful

  10. With Gottlieb beyond Gottlieb: The Role of Epigenetics in Psychobiological Development

    Science.gov (United States)

    Lux, Vanessa

    2013-01-01

    The emerging field of molecular epigenetics studies relatively stable changes in genetic activity that are not due to changes in the DNA sequence. Initial research results indicate a functional role for epigenetic mechanisms in neuron development and neuronal cell function. However, concepts that integrate these findings in an overall theory of…

  11. [Application of Epigenetics in Perinatal Nursing Care].

    Science.gov (United States)

    Chou, Hsueh-Fen; Kao, Chien-Huei; Gau, Meei-Ling

    2017-04-01

    Epigenetics is a field of biomedicine that expanded tremendously during the 1980s. Epigenetics is the study of heritable changes in gene expression independent of underlying DNA (DeoxyriboNucleic Acid) sequence, which not only affect this generation but will be passed to subsequent generations. Although conception is the critical moment for making decisions regarding gene mapping and fetal health, studies have shown that perinatal nursing care practices also affect the genetic remodeling processes and the subsequent health of the mother and her offspring. To optimize maternal-infant and the offspring health, it is important to ensure that the new mother get adequate nutrition, reduce stress levels, adopt gentle birth practices, facilitate exclusive breastfeeding, and avoid contacting toxic substances.

  12. [Epigenetics of prostate cancer].

    Science.gov (United States)

    Yi, Xiao-Ming; Zhou, Wen-Quan

    2010-07-01

    Prostate cancer is one of the most common malignant tumors in males, and its etiology and pathogenesis remain unclear. Epigenesis is involved in prostate cancer at all stages of the process, and closely related with its growth and metastasis. DNA methylation and histone modification are the most important manifestations of epigenetics in prostate cancer. The mechanisms of carcinogenesis of DNA methylation include whole-genome hypomethylation, aberrant local hypermethylation of promoters and genomic instability. DNA methylation is closely related to the process of prostate cancer, as in DNA damage repair, hormone response, tumor cell invasion/metastasis, cell cycle regulation, and so on. Histone modification causes corresponding changes in chromosome structure and the level of gene transcription, and it may affect the cycle, differentiation and apoptosis of cells, resulting in prostate cancer. Some therapies have been developed targeting the epigenetic changes in prostate cancer, including DNA methyltransferases and histone deacetylase inhibitors, and have achieved certain desirable results.

  13. Epigenetics and Autism

    OpenAIRE

    Mbadiwe, Tafari; Millis, Richard M.

    2013-01-01

    This review identifies mechanisms for altering DNA-histone interactions of cell chromatin to upregulate or downregulate gene expression that could serve as epigenetic targets for therapeutic interventions in autism. DNA methyltransferases (DNMTs) can phosphorylate histone H3 at T6. Aided by protein kinase C ? 1, the DNMT lysine-specific demethylase-1 prevents demethylation of H3 at K4. During androgen-receptor-(AR-) dependent gene activation, this sequence may produce AR-dependent gene overac...

  14. [Epigenetics and obesity].

    Science.gov (United States)

    Casanello, Paola; Krause, Bernardo J; Castro-Rodríguez, José A; Uauy, Ricardo

    Current evidence supports the notion that exposure to various environmental conditions in early life may induce permanent changes in the epigenome that persist throughout the life-course. This article focuses on early changes associated with obesity in adult life. A review is presented on the factors that induce changes in whole genome (DNA) methylation in early life that are associated with adult onset obesity and related disorders. In contrast, reversal of epigenetic changes associated with weight loss in obese subjects has not been demonstrated. This contrasts with well-established associations found between obesity related DNA methylation patterns at birth and adult onset obesity and diabetes. Epigenetic markers may serve to screen indivuals at risk for obesity and assess the effects of interventions in early life that may delay or prevent obesity in early life. This might contribute to lower the obesity-related burden of death and disability at the population level. The available evidence indicates that epigenetic marks are in fact modifiable, based on modifications in the intrauterine environment and changes in food intake, physical activity and dietary patterns patterns during pregnancy and early years of adult life. This offers the opportunity to intervene before conception, during pregnancy, infancy, childhood, and also in later life. There must be documentation on the best preventive actions in terms of diet and physical activity that will modify or revert the adverse epigenetic markers, thus preventing obesity and diabetes in suceptible individuals and populations. Copyright © 2016 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. Epigenetics and human obesity.

    Science.gov (United States)

    van Dijk, S J; Molloy, P L; Varinli, H; Morrison, J L; Muhlhausler, B S

    2015-01-01

    Recent technological advances in epigenome profiling have led to an increasing number of studies investigating the role of the epigenome in obesity. There is also evidence that environmental exposures during early life can induce persistent alterations in the epigenome, which may lead to an increased risk of obesity later in life. This paper provides a systematic review of studies investigating the association between obesity and either global, site-specific or genome-wide methylation of DNA. Studies on the impact of pre- and postnatal interventions on methylation and obesity are also reviewed. We discuss outstanding questions, and introduce EpiSCOPE, a multidisciplinary research program aimed at increasing the understanding of epigenetic changes in emergence of obesity. An electronic search for relevant articles, published between September 2008 and September 2013 was performed. From the 319 articles identified, 46 studies were included and reviewed. The studies provided no consistent evidence for a relationship between global methylation and obesity. The studies did identify multiple obesity-associated differentially methylated sites, mainly in blood cells. Extensive, but small, alterations in methylation at specific sites were observed in weight loss intervention studies, and several associations between methylation marks at birth and later life obesity were found. Overall, significant progress has been made in the field of epigenetics and obesity and the first potential epigenetic markers for obesity that could be detected at birth have been identified. Eventually this may help in predicting an individual's obesity risk at a young age and opens possibilities for introducing targeted prevention strategies. It has also become clear that several epigenetic marks are modifiable, by changing the exposure in utero, but also by lifestyle changes in adult life, which implies that there is the potential for interventions to be introduced in postnatal life to modify

  16. Epigenetics, Darwin, and Lamarck.

    Science.gov (United States)

    Penny, David

    2015-05-29

    It is not really helpful to consider modern environmental epigenetics as neo-Lamarckian; and there is no evidence that Lamarck considered the idea original to himself. We must all keep learning about inheritance, but attributing modern ideas to early researchers is not helpful, and can be misleading. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  17. Considering Maternal Dietary Modulators for Epigenetic Regulation and Programming of the Fetal Epigenome

    Directory of Open Access Journals (Sweden)

    Abalo Chango

    2015-04-01

    Full Text Available Fetal life is characterized by a tremendous plasticity and ability to respond to various environmental and lifestyle factors, including maternal nutrition. Identification of the role of dietary factors that can modulate and reshape the cellular epigenome during development, including methyl group donors (e.g., folate, choline and bioactive compounds (e.g., polyphenols is of great importance; however, there is insufficient knowledge of a particular effect of each type of modulator and/or their combination on fetal life. To enhance the quality and safety of food products for proper fetal health and disease prevention in later life, a better understanding of the underlying mechanisms of dietary epigenetic modulators during the critical prenatal period is necessary. This review focuses on the influence of maternal dietary components on DNA methylation, histone modification, and microRNAs, and summarizes current knowledge of the effect and importance of dietary components on epigenetic mechanisms that control the proper expression of genetic information. Evidence reveals that some components in the maternal diet can directly or indirectly affect epigenetic mechanisms. Understanding the underlying mechanisms of how early-life nutritional environment affects the epigenome during development is of great importance for the successful prevention of adult chronic diseases through optimal maternal nutrition.

  18. Considering maternal dietary modulators for epigenetic regulation and programming of the fetal epigenome.

    Science.gov (United States)

    Chango, Abalo; Pogribny, Igor P

    2015-04-14

    Fetal life is characterized by a tremendous plasticity and ability to respond to various environmental and lifestyle factors, including maternal nutrition. Identification of the role of dietary factors that can modulate and reshape the cellular epigenome during development, including methyl group donors (e.g., folate, choline) and bioactive compounds (e.g., polyphenols) is of great importance; however, there is insufficient knowledge of a particular effect of each type of modulator and/or their combination on fetal life. To enhance the quality and safety of food products for proper fetal health and disease prevention in later life, a better understanding of the underlying mechanisms of dietary epigenetic modulators during the critical prenatal period is necessary. This review focuses on the influence of maternal dietary components on DNA methylation, histone modification, and microRNAs, and summarizes current knowledge of the effect and importance of dietary components on epigenetic mechanisms that control the proper expression of genetic information. Evidence reveals that some components in the maternal diet can directly or indirectly affect epigenetic mechanisms. Understanding the underlying mechanisms of how early-life nutritional environment affects the epigenome during development is of great importance for the successful prevention of adult chronic diseases through optimal maternal nutrition.

  19. Comprehension and Data-Sharing Behavior of Direct-To-Consumer Genetic Test Customers.

    Science.gov (United States)

    McGrath, Scott P; Coleman, Jason; Najjar, Lotfollah; Fruhling, Ann; Bastola, Dhundy R

    2016-01-01

    The aim of this study was to evaluate current direct-to-consumer (DTC) genetic customers' ability to interpret and comprehend test results and to determine if honest brokers are needed. One hundred and twenty-two customers of the DTC genetic testing company 23andMe were polled in an online survey. The subjects were asked about their personal test results and to interpret the results of two mock test cases (type 2 diabetes and multiple sclerosis), where results were translated into disease probability for an individual compared to the public. When asked to evaluate the risk, 72.1% correctly assessed the first case and 77% were correct on the second case. Only 23.8% of those surveyed were able to interpret both cases correctly. x03C7;2 and logistic regression were used to interpret the results. Participants who took the time to read the DTC test-provided supplemental material were 3.93 times (p = 0.040) more likely to correctly interpret the test results than those who did not. The odds for correctly interpreting the test cases were 3.289 times (p = 0.011) higher for those who made more than USD 50,000 than those who made less. Survey results were compared to the Health Information National Trends Survey (HINTS) phase 4 cycle 3 data to evaluate national trends. Most of the subjects were able to correctly interpret the test cases, yet a majority did not share their results with a health-care professional. As the market for DTC genetic testing grows, test comprehension will become more critical. Involving more health professionals in this process may be necessary to ensure proper interpretations. © 2016 S. Karger AG, Basel.

  20. An update on the epigenetics of psychotic diseases and autism.

    Science.gov (United States)

    Abdolmaleky, Hamid Mostafavi; Zhou, Jin-Rong; Thiagalingam, Sam

    2015-01-01

    The examination of potential roles of epigenetic alterations in the pathogenesis of psychotic diseases have become an essential alternative in recent years as genetic studies alone are yet to uncover major gene(s) for psychosis. Here, we describe the current state of knowledge from the gene-specific and genome-wide studies of postmortem brain and blood cells indicating that aberrant DNA methylation, histone modifications and dysregulation of micro-RNAs are linked to the pathogenesis of mental diseases. There is also strong evidence supporting that all classes of psychiatric drugs modulate diverse features of the epigenome. While comprehensive environmental and genetic/epigenetic studies are uncovering the origins, and the key genes/pathways affected in psychotic diseases, characterizing the epigenetic effects of psychiatric drugs may help to design novel therapies in psychiatry.

  1. Eusocial insects as emerging models for behavioural epigenetics.

    Science.gov (United States)

    Yan, Hua; Simola, Daniel F; Bonasio, Roberto; Liebig, Jürgen; Berger, Shelley L; Reinberg, Danny

    2014-10-01

    Understanding the molecular basis of how behavioural states are established, maintained and altered by environmental cues is an area of considerable and growing interest. Epigenetic processes, including methylation of DNA and post-translational modification of histones, dynamically modulate activity-dependent gene expression in neurons and can therefore have important regulatory roles in shaping behavioural responses to environmental cues. Several eusocial insect species - with their unique displays of behavioural plasticity due to age, morphology and social context - have emerged as models to investigate the genetic and epigenetic underpinnings of animal social behaviour. This Review summarizes recent studies in the epigenetics of social behaviour and offers perspectives on emerging trends and prospects for establishing genetic tools in eusocial insects.

  2. Race in an epigenetic time: thinking biology in the plural.

    Science.gov (United States)

    Meloni, Maurizio

    2017-09-01

    The notion that biological memories of environmental experiences can be embedded in the human genome and even transmitted transgenerationally is increasingly relevant in the postgenomic world, particularly in molecular epigenetics, where the genome is conceptualized as porous to environmental signals. In this article I discuss the current rethinking of race in epigenetic rather than genetic terms, emphasizing some of its paradoxical implications, especially for public policy. I claim in particular that: (i) if sociologists want to investigate race in a postgenomic world they should pay more attention to this novel plastic and biosocial view of race; and (ii) there are no reasons to believe that an epigenetic view will extinguish race, or that soft-inheritance claims will produce a less exclusionary discourse than genetics (hard heredity). Quite the opposite, the ground for a re-racialization of social debates and the reinforcement of biological boundaries between groups are highlighted in the article. © London School of Economics and Political Science 2017.

  3. Assessment of Direct-to-Consumer Genetic Testing Policy in Korea Based on Consumer Preference.

    Science.gov (United States)

    Jeong, Gicheol

    2017-01-01

    In June 2016, Korea permitted direct-to-consumer genetic testing (DTC-GT) on 42 genes. However, both the market and industry have not yet been fully activated. Considering the aforementioned context, this study provides important insights. The Korean DTC-GT policy assessment is based on consumer preference analysis using a discrete choice experiment. In August 2016, a web-based survey was conducted to collect data from 1,200 respondents. The estimation results show that consumers prefer a DTC-GT product that is cheap, tests various items or genes, offers accurate test results, and guarantees the confidentiality of all information. However, consumers are not entirely satisfied by current DTC-GT products due to the existence of insufficient and/or inadequate policies. First, the permitted testing of 42 genes is insufficient to satisfy consumers' curiosity regarding their genes. Second, the accuracy of the DTC-GT products has not been fully verified, assessed, and communicated to consumers. Finally, regulatory loopholes that allow information leaks in the DTC-GT process can occur. These findings imply that DTC-GT requires an improvement in government policy-making criteria and the implementation of practical measures to guarantee test accuracy and genetic information. © 2017 S. Karger AG, Basel.

  4. Journal of Genetics | Indian Academy of Sciences

    Indian Academy of Sciences (India)

    Keywords. cytosine methylation; DNA methylation mechanisms; DNA demethylation mechanisms; Darwinian-cum-Lamarckian evolution; epialleles; epigenetic modifications; genetic recombination; heritable induced defence; mutational hotspots; transgenerational inheritance.

  5. Mapping the Plasticity of the E. coli Genetic Code with Orthogonal Pair Directed Sense Codon Reassignment.

    Science.gov (United States)

    Schmitt, Margaret A; Biddle, Wil; Fisk, John Domenic

    2018-04-18

    The relative quantitative importance of the factors that determine the fidelity of translation is largely unknown, which makes predicting the extent to which the degeneracy of the genetic code can be broken challenging. Our strategy of using orthogonal tRNA/aminoacyl tRNA synthetase pairs to precisely direct the incorporation of a single amino acid in response to individual sense and nonsense codons provides a suite of related data with which to examine the plasticity of the code. Each directed sense codon reassignment measurement is an in vivo competition experiment between the introduced orthogonal translation machinery and the natural machinery in E. coli. This report discusses 20 new, related genetic codes, in which a targeted E. coli wobble codon is reassigned to tyrosine utilizing the orthogonal tyrosine tRNA/aminoacyl tRNA synthetase pair from Methanocaldococcus jannaschii. One at a time, reassignment of each targeted sense codon to tyrosine is quantified in cells by measuring the fluorescence of GFP variants in which the essential tyrosine residue is encoded by a non-tyrosine codon. Significantly, every wobble codon analyzed may be partially reassigned with efficiencies ranging from 0.8% to 41%. The accumulation of the suite of data enables a qualitative dissection of the relative importance of the factors affecting the fidelity of translation. While some correlation was observed between sense codon reassignment and either competing endogenous tRNA abundance or changes in aminoacylation efficiency of the altered orthogonal system, no single factor appears to predominately drive translational fidelity. Evaluation of relative cellular fitness in each of the 20 quantitatively-characterized proteome-wide tyrosine substitution systems suggests that at a systems level, E. coli is robust to missense mutations.

  6. Genetically-directed, cell type-specific sparse labeling for the analysis of neuronal morphology.

    Directory of Open Access Journals (Sweden)

    Thomas Rotolo

    Full Text Available In mammals, genetically-directed cell labeling technologies have not yet been applied to the morphologic analysis of neurons with very large and complex arbors, an application that requires extremely sparse labeling and that is only rendered practical by limiting the labeled population to one or a few predetermined neuronal subtypes.In the present study we have addressed this application by using CreER technology to non-invasively label very small numbers of neurons so that their morphologies can be fully visualized. Four lines of IRES-CreER knock-in mice were constructed to permit labeling selectively in cholinergic or catecholaminergic neurons [choline acetyltransferase (ChAT-IRES-CreER or tyrosine hydroxylase (TH-IRES-CreER], predominantly in projection neurons [neurofilament light chain (NFL-IRES-CreER], or broadly in neurons and some glia [vesicle-associated membrane protein2 (VAMP2-IRES-CreER]. When crossed to the Z/AP reporter and exposed to 4-hydroxytamoxifen in the early postnatal period, the number of neurons expressing the human placental alkaline phosphatase reporter can be reproducibly lowered to fewer than 50 per brain. Sparse Cre-mediated recombination in ChAT-IRES-CreER;Z/AP mice shows the full axonal and dendritic arbors of individual forebrain cholinergic neurons, the first time that the complete morphologies of these very large neurons have been revealed in any species.Sparse genetically-directed, cell type-specific neuronal labeling with IRES-creER lines should prove useful for studying a wide variety of questions in neuronal development and disease.

  7. Epigenetics in women's health care.

    Science.gov (United States)

    Pozharny, Yevgeniya; Lambertini, Luca; Clunie, Garfield; Ferrara, Lauren; Lee, Men-Jean

    2010-01-01

    Epigenetics refers to structural modifications to genes that do not change the nucleotide sequence itself but instead control and regulate gene expression. DNA methylation, histone modification, and RNA regulation are some of the mechanisms involved in epigenetic modification. Epigenetic changes are believed to be a result of changes in an organism's environment that result in fixed and permanent changes in most differentiated cells. Some environmental changes that have been linked to epigenetic changes include starvation, folic acid, and various chemical exposures. There are periods in an organism's life cycle in which the organism is particularly susceptible to epigenetic influences; these include fertilization, gametogenesis, and early embryo development. These are also windows of opportunity for interventions during the reproductive life cycle of women to improve maternal-child health. New data suggest that epigenetic influences might be involved in the regulation of fetal development and the pathophysiology of adult diseases such as cancer, diabetes, obesity, and neurodevelopmental disorders. Various epigenetic mechanisms may also be involved in the pathogenesis of preeclampsia and intrauterine growth restriction. Additionally, environmental exposures are being held responsible for causing epigenetic changes that lead to a disease process. Exposure to heavy metals, bioflavonoids, and endocrine disruptors, such as bisphenol A and phthalates, has been shown to affect the epigenetic memory of an organism. Their long-term effects are unclear at this point, but many ongoing studies are attempting to elucidate the pathophysiological effects of such gene-environment interactions. (c) 2010 Mount Sinai School of Medicine.

  8. Epigenetic game theory: How to compute the epigenetic control of maternal-to-zygotic transition

    Science.gov (United States)

    Wang, Qian; Gosik, Kirk; Xing, Sujuan; Jiang, Libo; Sun, Lidan; Chinchilli, Vernon M.; Wu, Rongling

    2017-03-01

    Epigenetic reprogramming is thought to play a critical role in maintaining the normal development of embryos. How the methylation state of paternal and maternal genomes regulates embryogenesis depends on the interaction and coordination of the gametes of two sexes. While there is abundant research in exploring the epigenetic interactions of sperms and oocytes, a knowledge gap exists in the mechanistic quantitation of these interactions and their impact on embryo development. This review aims at formulating a modeling framework to address this gap through the integration and synthesis of evolutionary game theory and the latest discoveries of the epigenetic control of embryo development by next-generation sequencing. This framework, named epigenetic game theory or epiGame, views embryogenesis as an ecological system in which two highly distinct and specialized gametes coordinate through either cooperation or competition, or both, to maximize the fitness of embryos under Darwinian selection. By implementing a system of ordinary differential equations, epiGame quantifies the pattern and relative magnitude of the methylation effects on embryogenesis by the mechanisms of cooperation and competition. epiGame may gain new insight into reproductive biology and can be potentially applied to design personalized medicines for genetic disorder intervention.

  9. Epigenetic game theory: How to compute the epigenetic control of maternal-to-zygotic transition.

    Science.gov (United States)

    Wang, Qian; Gosik, Kirk; Xing, Sujuan; Jiang, Libo; Sun, Lidan; Chinchilli, Vernon M; Wu, Rongling

    2017-03-01

    Epigenetic reprogramming is thought to play a critical role in maintaining the normal development of embryos. How the methylation state of paternal and maternal genomes regulates embryogenesis depends on the interaction and coordination of the gametes of two sexes. While there is abundant research in exploring the epigenetic interactions of sperms and oocytes, a knowledge gap exists in the mechanistic quantitation of these interactions and their impact on embryo development. This review aims at formulating a modeling framework to address this gap through the integration and synthesis of evolutionary game theory and the latest discoveries of the epigenetic control of embryo development by next-generation sequencing. This framework, named epigenetic game theory or epiGame, views embryogenesis as an ecological system in which two highly distinct and specialized gametes coordinate through either cooperation or competition, or both, to maximize the fitness of embryos under Darwinian selection. By implementing a system of ordinary differential equations, epiGame quantifies the pattern and relative magnitude of the methylation effects on embryogenesis by the mechanisms of cooperation and competition. epiGame may gain new insight into reproductive biology and can be potentially applied to design personalized medicines for genetic disorder intervention. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Epigenetics in Medullary Thyroid Cancer: From Pathogenesis to Targeted Therapy.

    Science.gov (United States)

    Vitale, Giovanni; Dicitore, Alessandra; Messina, Erika; Sciammarella, Concetta; Faggiano, Antongiulio; Colao, Annamaria

    2016-01-01

    Medullary thyroid carcinoma (MTC) originates from the parafollicular C cells of the thyroid gland. Mutations of the RET proto-oncogene are implicated in the pathogenesis of MTC. Germline activating mutations of this gene have been reported in about 88-98% of familial MTCs, while somatic mutations of RET gene have been detected in about 23-70% of sporadic forms. Although these genetic events are well characterized, much less is known about the role of epigenetic abnormalities in MTC. The present review reports a detailed description of epigenetic abnormalities (DNA methylation, histone modifications and miRNA profile), probably involved in the pathogenesis and progression of MTC. A systematic review was performed using Pubmed and Google patents databases. We report the current understanding of epigenetic patterns in MTC and discuss the potential use of current knowledge in designing novel therapeutic strategies through epigenetic drugs, focusing on recent patents in this field. Taking into account the reversibility of epigenetic alterations and the recent development in this field, epigenetic therapy may emerge for clinical use in the near future for patients with advanced MTC.

  11. Dietary factors and epigenetic regulation for prostate cancer prevention.

    Science.gov (United States)

    Ho, Emily; Beaver, Laura M; Williams, David E; Dashwood, Roderick H

    2011-11-01

    The role of epigenetic alterations in various human chronic diseases has gained increasing attention and has resulted in a paradigm shift in our understanding of disease susceptibility. In the field of cancer research, e.g., genetic abnormalities/mutations historically were viewed as primary underlying causes; however, epigenetic mechanisms that alter gene expression without affecting DNA sequence are now recognized as being of equal or greater importance for oncogenesis. Methylation of DNA, modification of histones, and interfering microRNA (miRNA) collectively represent a cadre of epigenetic elements dysregulated in cancer. Targeting the epigenome with compounds that modulate DNA methylation, histone marks, and miRNA profiles represents an evolving strategy for cancer chemoprevention, and these approaches are starting to show promise in human clinical trials. Essential micronutrients such as folate, vitamin B-12, selenium, and zinc as well as the dietary phytochemicals sulforaphane, tea polyphenols, curcumin, and allyl sulfur compounds are among a growing list of agents that affect epigenetic events as novel mechanisms of chemoprevention. To illustrate these concepts, the current review highlights the interactions among nutrients, epigenetics, and prostate cancer susceptibility. In particular, we focus on epigenetic dysregulation and the impact of specific nutrients and food components on DNA methylation and histone modifications that can alter gene expression and influence prostate cancer progression.

  12. Genetic parameters for direct and maternal calving ease in Walloon dairy cattle based on linear and threshold models.

    Science.gov (United States)

    Vanderick, S; Troch, T; Gillon, A; Glorieux, G; Gengler, N

    2014-12-01

    Calving ease scores from Holstein dairy cattle in the Walloon Region of Belgium were analysed using univariate linear and threshold animal models. Variance components and derived genetic parameters were estimated from a data set including 33,155 calving records. Included in the models were season, herd and sex of calf × age of dam classes × group of calvings interaction as fixed effects, herd × year of calving, maternal permanent environment and animal direct and maternal additive genetic as random effects. Models were fitted with the genetic correlation between direct and maternal additive genetic effects either estimated or constrained to zero. Direct heritability for calving ease was approximately 8% with linear models and approximately 12% with threshold models. Maternal heritabilities were approximately 2 and 4%, respectively. Genetic correlation between direct and maternal additive effects was found to be not significantly different from zero. Models were compared in terms of goodness of fit and predictive ability. Criteria of comparison such as mean squared error, correlation between observed and predicted calving ease scores as well as between estimated breeding values were estimated from 85,118 calving records. The results provided few differences between linear and threshold models even though correlations between estimated breeding values from subsets of data for sires with progeny from linear model were 17 and 23% greater for direct and maternal genetic effects, respectively, than from threshold model. For the purpose of genetic evaluation for calving ease in Walloon Holstein dairy cattle, the linear animal model without covariance between direct and maternal additive effects was found to be the best choice. © 2014 Blackwell Verlag GmbH.

  13. Communication is the key. : Part 2 : Direct to consumer genetics in our future daily life ?

    Science.gov (United States)

    Perbal, Bernard

    2014-12-01

    The considerable advances of genome sequencing over the past decades have had a profound impact on our daily life and opened up new avenues for the public to have access to their genetic information and learn more about their ancestry, genealogy and other traits that make each of us unique individuals. A very large number of individual single nucleotide polymorphisms (SNPs) have been associated to diseases whereas others have no known phenotype. For example, among the SNPs mapped within ccn1(cyr61), ccn2(ctgf), ccn3(nov), ccn4(wisp-1), ccn5(wisp-2) and ccn6 (wisp-3), only mutations within ccn4 were associated to PPD (the autosomal recessive skeletal disorder Progressive Pseudorheumatoid Dysplasia). On the occasion of this JCCS special issue on the roles of hormetic responses in adaptation, and response of living species to the modifications of their environment, it appeared that it was a good time to briefly review a topic that has been the subject of passionate discussions for the past few years, that is Direct to Consumer genetic tests (DTC GT). Based on the use of DNA analysis and identification of polymorphisms, DTC GT have been developed by several companies in the USA and in countries where there was no legal obstacle for customers to have direct access to their genetic information and manage their healthcare. Problems that arose and decisions that have been taken by regulatory agencies are presented and discussed in this editorial. The « freeze » of health-oriented DTC GT in the USA neither implies the end of DNA analysis nor « fun » applications, which are not aimed at providing risks estimates for particular illnesses. As shown in the example which is discussed in this editorial, DTC GT for cosmetic applications might be considered a fun application of great interest for companies such as L'Oréal, who recently developed the Makeup Genius mobile application. Other fun applications of DTC GT are discussed but there is no doubt that nothing will stop

  14. Natural epigenetic variation contributes to heritable flowering divergence in a widespread asexual dandelion lineage

    Czech Academy of Sciences Publication Activity Database

    Wilschut, R. A.; Oplaat, C.; Snoek, L. B.; Kirschner, Jan; Verhoeven, K. J. F.

    2016-01-01

    Roč. 25, č. 8 (2016), s. 1759-1768 ISSN 0962-1083 Institutional support: RVO:67985939 Keywords : apomixis * epigenetic s * Taraxacum Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.086, year: 2016

  15. General-Purpose Genotype or How Epigenetics Extend the Flexibility of a Genotype

    Directory of Open Access Journals (Sweden)

    Rachel Massicotte

    2012-01-01

    Full Text Available This project aims at investigating the link between individual epigenetic variability (not related to genetic variability and the variation of natural environmental conditions. We studied DNA methylation polymorphisms of individuals belonging to a single genetic lineage of the clonal diploid fish Chrosomus eos-neogaeus sampled in seven geographically distant lakes. In spite of a low number of informative fragments obtained from an MSAP analysis, individuals of a given lake are epigenetically similar, and methylation profiles allow the clustering of individuals in two distinct groups of populations among lakes. More importantly, we observed a significant pH variation that is consistent with the two epigenetic groups. It thus seems that the genotype studied has the potential to respond differentially via epigenetic modifications under variable environmental conditions, making epigenetic processes a relevant molecular mechanism contributing to phenotypic plasticity over variable environments in accordance with the GPG model.

  16. Epigenetic codes programming class switch recombination

    Directory of Open Access Journals (Sweden)

    Bharat eVaidyanathan

    2015-09-01

    Full Text Available Class switch recombination imparts B cells with a fitness-associated adaptive advantage during a humoral immune response by using a precision-tailored DNA excision and ligation process to swap the default constant region gene of the antibody with a new one that has unique effector functions. This secondary diversification of the antibody repertoire is a hallmark of the adaptability of B cells when confronted with environmental and pathogenic challenges. Given that the nucleotide sequence of genes during class switching remains unchanged (genetic constraints, it is logical and necessary therefore, to integrate the adaptability of B cells to an epigenetic state, which is dynamic and can be heritably modulated before, after or even during an antibody-dependent immune response. Epigenetic regulation encompasses heritable changes that affect function (phenotype without altering the sequence information embedded in a gene, and include histone, DNA and RNA modifications. Here, we review current literature on how B cells use an epigenetic code language as a means to ensure antibody plasticity in light of pathogenic insults.

  17. New Genetics

    Science.gov (United States)

    ... of the booklet. » more Chapter 1: How Genes Work Covers DNA, RNA, transcription, RNA splicing, translation, ribosomes, antibiotics, genetic diseases, gene chips. » more Chapter 2: RNA and DNA Revealed: New Roles, New Rules Covers microRNAs, RNAi, epigenetics, telomeres, mtDNA, recombinant DNA. » ...

  18. Parental epigenetic difference in DNA methylation-level may play ...

    African Journals Online (AJOL)

    Parental epigenetic difference in DNA methylation-level may play contrasting roles for different agronomic traits related to yield heterosis in maize. ... or hybrid vigor has been exploited to nearly the fullest extent, the molecular and genetic basis underlying this remarkable biological phenomenon remains largely an enigma.

  19. Distinct patterns of epigenetic marks and transcription factor binding ...

    Indian Academy of Sciences (India)

    Distinct patterns of epigenetic marks and transcription factor binding sites across promoters of sense-intronic long noncoding RNAs. Sourav Ghosh, Satish Sati, Shantanu Sengupta and Vinod Scaria. J. Genet. 94, 17–25. Gencode V9 lncRNA gene : 11004. Known lncRNA : 1175. Novel lncRNA : 5898. Putative lncRNA :.

  20. Using an Active-Learning Approach to Teach Epigenetics

    Science.gov (United States)

    Colon-Berlingeri, Migdalisel

    2010-01-01

    Epigenetics involves heritable changes in gene expression that do not involve alterations in the DNA sequence. I developed an active-learning approach to convey this topic to students in a college genetics course. I posted a brief summary of the topic before class to stimulate exchange in cooperative groups. During class, we discussed the…

  1. Neonatal imitation and an epigenetic account of mirror neuron development.

    Science.gov (United States)

    Simpson, Elizabeth A; Fox, Nathan A; Tramacere, Antonella; Ferrari, Pier F

    2014-04-01

    Neonatal imitation should not exclusively be considered at the population-level; instead, we propose that inconsistent findings regarding its occurrence result from important individual differences in imitative responses. We also highlight what we consider to be a false dichotomy of genetic versus learning accounts of the development of mirror neurons, and instead suggest a more parsimonious epigenetic perspective.

  2. The ascent of acetylation in the epigenetics of rheumatoid arthritis

    NARCIS (Netherlands)

    Grabiec, Aleksander M.; Reedquist, Kris A.

    2013-01-01

    Genome-wide association studies have shown that genetic polymorphisms make a substantial but incomplete contribution to the risk of developing rheumatoid arthritis (RA). Efforts to understand the nongenetic contributions to RA disease susceptibility have recently focused on the study of epigenetic

  3. ATM directs DNA damage responses and proteostasis via genetically separable pathways.

    Science.gov (United States)

    Lee, Ji-Hoon; Mand, Michael R; Kao, Chung-Hsuan; Zhou, Yi; Ryu, Seung W; Richards, Alicia L; Coon, Joshua J; Paull, Tanya T

    2018-01-09

    The protein kinase ATM is a master regulator of the DNA damage response but also responds directly to oxidative stress. Loss of ATM causes ataxia telangiectasia, a neurodegenerative disorder with pleiotropic symptoms that include cerebellar dysfunction, cancer, diabetes, and premature aging. We genetically separated the activation of ATM by DNA damage from that by oxidative stress using separation-of-function mutations. We found that deficient activation of ATM by the Mre11-Rad50-Nbs1 complex and DNA double-strand breaks resulted in loss of cell viability, checkpoint activation, and DNA end resection in response to DNA damage. In contrast, loss of oxidative activation of ATM had minimal effects on DNA damage-related outcomes but blocked ATM-mediated initiation of checkpoint responses after oxidative stress and resulted in deficiencies in mitochondrial function and autophagy. In addition, expression of a variant ATM incapable of activation by oxidative stress resulted in widespread protein aggregation. These results indicate a direct relationship between the mechanism of ATM activation and its effects on cellular metabolism and DNA damage responses in human cells and implicate ATM in the control of protein homeostasis. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  4. Evolution of branched regulatory genetic pathways: directional selection on pleiotropic loci accelerates developmental system drift.

    Science.gov (United States)

    Johnson, Norman A; Porter, Adam H

    2007-01-01

    Developmental systems are regulated by a web of interacting loci. One common and useful approach in studying the evolution of development is to focus on classes of interacting elements within these systems. Here, we use individual-based simulations to study the evolution of traits controlled by branched developmental pathways involving three loci, where one locus regulates two different traits. We examined the system under a variety of selective regimes. In the case where one branch was under stabilizing selection and the other under directional selection, we observed "developmental system drift": the trait under stabilizing selection showed little phenotypic change even though the loci underlying that trait showed considerable evolutionary divergence. This occurs because the pleiotropic locus responds to directional selection and compensatory mutants are then favored in the pathway under stabilizing selection. Though developmental system drift may be caused by other mechanisms, it seems likely that it is accelerated by the same underlying genetic mechanism as that producing the Dobzhansky-Muller incompatibilities that lead to speciation in both linear and branched pathways. We also discuss predictions of our model for developmental system drift and how different selective regimes affect probabilities of speciation in the branched pathway system.

  5. Epigenetics primer: why the clinician should care about epigenetics.

    Science.gov (United States)

    Duarte, Julio D

    2013-12-01

    Epigenetics describes heritable alterations of gene expression that do not involve DNA sequence variation and are changeable throughout an organism's lifetime. Not only can epigenetic status influence drug response, but it can also be modulated by drugs. In this review, the three major epigenetic mechanisms are described: covalent DNA modification, histone protein modification, and regulation by noncoding RNA. Further, this review describes how drug therapy can influence, and be influenced by, these mechanisms. Drugs with epigenetic mechanisms are already in use, with many more likely to be approved within the next few years. As the understanding of epigenetic processes improves, so will the ability to use these data in the clinic to improve patient care. © 2013 Pharmacotherapy Publications, Inc.

  6. Epigenetic Differentiation of Natural Populations of Lilium bosniacum Associated with Contrasting Habitat Conditions

    OpenAIRE

    Zoldoš, Vlatka; Biruš, Ivan; Muratović, Edina; Šatović, Zlatko; Vojta, Aleksandar; Robin, Odile; Pustahija, Fatima; Bogunić, Faruk; Vičić Bočkor, Vedrana; Siljak-Yakovlev, Sonja

    2018-01-01

    Abstract Epigenetic variation in natural populations with contrasting habitats might be an important element, in addition to the genetic variation, in plant adaptation to environmental stress. Here, we assessed genetic, epigenetic, and cytogenetic structure of the three Lilium bosniacum populations growing on distinct habitats. One population was growing under habitual ecological conditions for this species and the other two were growing under stress associated with high altitude and serpenti...

  7. Rural-urban and racial-ethnic differences in awareness of direct-to-consumer genetic testing.

    Science.gov (United States)

    Salloum, Ramzi G; George, Thomas J; Silver, Natalie; Markham, Merry-Jennifer; Hall, Jaclyn M; Guo, Yi; Bian, Jiang; Shenkman, Elizabeth A

    2018-02-23

    Access to direct-to-consumer genetic testing services has increased in recent years. However, disparities in knowledge and awareness of these services are not well documented. We examined awareness of genetic testing services by rural/urban and racial/ethnic status. Analyses were conducted using pooled cross-sectional data from 4 waves (2011-2014) of the Health Information National Trends Survey (HINTS). Descriptive statistics compared sample characteristics and information sources by rural/urban residence. Logistic regression was used to examine the relationship between geography, racial/ethnic status, and awareness of genetic testing, controlling for sociodemographic characteristics. Of 13,749 respondents, 16.7% resided in rural areas, 13.8% were Hispanic, and 10.1% were non-Hispanic black. Rural residents were less likely than urban residents to report awareness of genetic testing (OR = 0.74, 95% CI = 0.63-0.87). Compared with non-Hispanic whites, racial/ethnic minorities were less likely to be aware of genetic testing: Hispanic (OR = 0.68, 95% CI = 0.56-0.82); and non-Hispanic black (OR = 0.74, 95% CI = 0.61-0.90). Rural-urban and racial-ethnic differences exist in awareness of direct-to-consumer genetic testing. These differences may translate into disparities in the uptake of genetic testing, health behavior change, and disease prevention through precision and personalized medicine.

  8. [Epigenetics in allergic diseases and asthma].

    Science.gov (United States)

    Castro-Rodríguez, José A; Krause, Bernardo J; Uauy, Ricardo; Casanello, Paola

    2016-01-01

    Allergic diseases and asthma are the result of complex interactions between genetic predisposition and environmental factors. Asthma is one of the most prevalent chronic disease among children. In this article we review some environmental factors like: allergen exposition, tobacco, bacteria, microbial components, diet, obesity and stress, which influences during intrauterine and infancy life in the epigenetic regulation of asthma and allergic diseases. The review has been done in three models: in-vitro, animal and human. Copyright © 2016 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  9. Epigenetic control of CD8+ T cell differentiation.

    Science.gov (United States)

    Henning, Amanda N; Roychoudhuri, Rahul; Restifo, Nicholas P

    2018-05-01

    Upon stimulation, small numbers of naive CD8 + T cells proliferate and differentiate into a variety of memory and effector cell types. CD8 + T cells can persist for years and kill tumour cells and virally infected cells. The functional and phenotypic changes that occur during CD8 + T cell differentiation are well characterized, but the epigenetic states that underlie these changes are incompletely understood. Here, we review the epigenetic processes that direct CD8 + T cell differentiation and function. We focus on epigenetic modification of DNA and associated histones at genes and their regulatory elements. We also describe structural changes in chromatin organization that affect gene expression. Finally, we examine the translational potential of epigenetic interventions to improve CD8 + T cell function in individuals with chronic infections and cancer.

  10. Nucleosome Positioning and Epigenetics

    Science.gov (United States)

    Schwab, David; Bruinsma, Robijn

    2008-03-01

    The role of chromatin structure in gene regulation has recently taken center stage in the field of epigenetics, phenomena that change the phenotype without changing the DNA sequence. Recent work has also shown that nucleosomes, a complex of DNA wrapped around a histone octamer, experience a sequence dependent energy landscape due to the variation in DNA bend stiffness with sequence composition. In this talk, we consider the role nucleosome positioning might play in the formation of heterochromatin, a compact form of DNA generically responsible for gene silencing. In particular, we discuss how different patterns of nucleosome positions, periodic or random, could either facilitate or suppress heterochromatin stability and formation.

  11. Epigenetics of kidney disease.

    Science.gov (United States)

    Wanner, Nicola; Bechtel-Walz, Wibke

    2017-07-01

    DNA methylation and histone modifications determine renal programming and the development and progression of renal disease. The identification of the way in which the renal cell epigenome is altered by environmental modifiers driving the onset and progression of renal diseases has extended our understanding of the pathophysiology of kidney disease progression. In this review, we focus on current knowledge concerning the implications of epigenetic modifications during renal disease from early development to chronic kidney disease progression including renal fibrosis, diabetic nephropathy and the translational potential of identifying new biomarkers and treatments for the prevention and therapy of chronic kidney disease and end-stage kidney disease.

  12. Transgenerational epigenetics: Inheritance of global cytosine methylation and methylation-related epigenetic markers in the shrub Lavandula latifolia.

    Science.gov (United States)

    Herrera, Carlos M; Alonso, Conchita; Medrano, Mónica; Pérez, Ricardo; Bazaga, Pilar

    2018-04-01

    The ecological and evolutionary significance of natural epigenetic variation (i.e., not based on DNA sequence variants) variation will depend critically on whether epigenetic states are transmitted from parents to offspring, but little is known on epigenetic inheritance in nonmodel plants. We present a quantitative analysis of transgenerational transmission of global DNA cytosine methylation (= proportion of all genomic cytosines that are methylated) and individual epigenetic markers (= methylation status of anonymous MSAP markers) in the shrub Lavandula latifolia. Methods based on parent-offspring correlations and parental variance component estimation were applied to epigenetic features of field-growing plants ('maternal parents') and greenhouse-grown progenies. Transmission of genetic markers (AFLP) was also assessed for reference. Maternal parents differed significantly in global DNA cytosine methylation (range = 21.7-36.7%). Greenhouse-grown maternal families differed significantly in global methylation, and their differences were significantly related to maternal origin. Methylation-sensitive amplified polymorphism (MSAP) markers exhibited significant transgenerational transmission, as denoted by significant maternal variance component of marker scores in greenhouse families and significant mother-offspring correlations of marker scores. Although transmission-related measurements for global methylation and MSAP markers were quantitatively lower than those for AFLP markers taken as reference, this study has revealed extensive transgenerational transmission of genome-wide global cytosine methylation and anonymous epigenetic markers in L. latifolia. Similarity of results for global cytosine methylation and epigenetic markers lends robustness to this conclusion, and stresses the value of considering both types of information in epigenetic studies of nonmodel plants. © 2018 Botanical Society of America.

  13. Epigenetics of host-pathogen interactions: the road ahead and the road behind.

    Directory of Open Access Journals (Sweden)

    Elena Gómez-Díaz

    Full Text Available A growing body of evidence points towards epigenetic mechanisms being responsible for a wide range of biological phenomena, from the plasticity of plant growth and development to the nutritional control of caste determination in honeybees and the etiology of human disease (e.g., cancer. With the (partial elucidation of the molecular basis of epigenetic variation and the heritability of certain of these changes, the field of evolutionary epigenetics is flourishing. Despite this, the role of epigenetics in shaping host-pathogen interactions has received comparatively little attention. Yet there is plenty of evidence supporting the implication of epigenetic mechanisms in the modulation of the biological interaction between hosts and pathogens. The phenotypic plasticity of many key parasite life-history traits appears to be under epigenetic control. Moreover, pathogen-induced effects in host phenotype may have transgenerational consequences, and the bases of these changes and their heritability probably have an epigenetic component. The significance of epigenetic modifications may, however, go beyond providing a mechanistic basis for host and pathogen plasticity. Epigenetic epidemiology has recently emerged as a promising area for future research on infectious diseases. In addition, the incorporation of epigenetic inheritance and epigenetic plasticity mechanisms to evolutionary models and empirical studies of host-pathogen interactions will provide new insights into the evolution and coevolution of these associations. Here, we review the evidence available for the role epigenetics on host-pathogen interactions, and the utility and versatility of the epigenetic technologies available that can be cross-applied to host-pathogen studies. We conclude with recommendations and directions for future research on the burgeoning field of epigenetics as applied to host-pathogen interactions.

  14. Microbiome, inflammation, epigenetic alterations, and mental diseases.

    Science.gov (United States)

    Alam, Reza; Abdolmaleky, Hamid M; Zhou, Jin-Rong

    2017-09-01

    Major mental diseases such as autism, bipolar disorder, schizophrenia, and major depressive disorder are debilitating illnesses with complex etiologies. Recent findings show that the onset and development of these illnesses cannot be well described by the one-gene; one-disease approach. Instead, their clinical presentation is thought to result from the regulative interplay of a large number of genes. Even though the involvement of many genes are likely, up regulating and activation or down regulation and silencing of these genes by the environmental factors play a crucial role in contributing to their pathogenesis. Much of this interplay may be moderated by epigenetic changes. Similar to genetic mutations, epigenetic modifications such as DNA methylation, histone modifications, and RNA interference can influence gene expression and therefore may cause behavioral and neuronal changes observed in mental disorders. Environmental factors such as diet, gut microbiota, and infections have significant role in these epigenetic modifications. Studies show that bioactive nutrients and gut microbiota can alter either DNA methylation and histone signatures through a variety of mechanisms. Indeed, microbes within the human gut may play a significant role in the regulation of various elements of "gut-brain axis," via their influence on inflammatory cytokines and production of antimicrobial peptides that affect the epigenome through their involvement in generating short chain fatty acids, vitamin synthesis, and nutrient absorption. In addition, they may participate in-gut production of many common neurotransmitters. In this review we will consider the potential interactions of diet, gastrointestinal microbiome, inflammation, and epigenetic alterations in psychiatric disorders. © 2017 Wiley Periodicals, Inc.

  15. The effect of direct-to-consumer genetic tests on anticipated affect and health-seeking behaviors: a pilot survey.

    Science.gov (United States)

    Bansback, Nick; Sizto, Sonia; Guh, Daphne; Anis, Aslam H

    2012-10-01

    Numerous websites offer direct-to-consumer (DTC) genetic testing, yet it is unknown how individuals will react to genetic risk profiles online. The objective of this study was to determine the feasibility of using a web-based survey and conjoint methods to elicit individuals' interpretations of genetic risk profiles by their anticipated worry/anxiousness and health-seeking behaviors. A web-based survey was developed using conjoint methods. Each survey presented 12 hypothetical genetic risk profiles describing genetic test results for four diseases. Test results were characterized by the type of disease (eight diseases), individual risk (five levels), and research confidence (three levels). After each profile, four questions were asked regarding anticipated worry and health-seeking behaviors. Probabilities of response outcomes based on attribute levels were estimated from logistic regression models, adjusting for covariates. Overall, 319 participants (69%) completed 3828 unique genetic risk profiles. Across all profiles, most participants anticipated making doctor's appointments (63%), lifestyle changes (57%), and accessing screening (57%); 40% anticipated feeling more worried and anxious. Higher levels of disease risk were significantly associated with affirmative responses. Conjoint methods may be used to elicit reactions to genetic information online. Preliminary results suggest that genetic information may increase worry/anxiousness and health-seeking behaviors among consumers of DTC tests. Further research is planned to determine the appropriateness of these affects and behaviors.

  16. Genetic Barrier to Direct Acting Antivirals in HCV Sequences Deposited in the European Databank.

    Directory of Open Access Journals (Sweden)

    Dimas Alexandre Kliemann

    Full Text Available Development of resistance results from mutations in the viral genome, and the presence of selective drug pressure leads to the emergence of a resistant virus population. The aim of this study was to analyze the impact of genetic variability on the genetic barrier to drug resistance to DAAs.The genetic barrier was quantified based on the number and type of nucleotide mutations required to impart resistance, considering full-length HCV NS3, NS5A and NS5B regions segregated by genotype into subtypes 1a, 1b, 2a, 2b and 3a. This study analyzeds 789 NS3 sequences, 708 sequences and 536 NS5B sequences deposited in the European Hepatitis C Virus Database, in the following resistance-associated positions: NS3: F43/I/L/S/V, Q80K/R, R155K/G, A156G/S/T and D168A/C/E/G/H/N/T/V/Y; NS5A: L/M28A/T/V, Q30E/H/R, L31F/I/M/V, H58D or P58S and Y93C/F/H/N/S; NS5B: S282P/R/T, C316H/N/Y, S368T, Y448C/H, S556G/R, D559R.Variants that require only one transversion in NS3 were found in 4 positions and include F43S, R80K, R155K/G and A156T. The genetic barrier to resistance shows subtypic differences at position 155 of the NS3 gene where a single transition is necessary in subtype 1a. In the NS5A gene, 5 positions where only one nucleotide change can confer resistance were found, such as L31M which requires one transversion in all subtypes, except in 0.28% of 1b sequences; and R30H, generated by a single transition, which was found in 10.25% of the sequences of genotype 1b. Other subtypic differences were observed at position 58, where resistance is less likely in genotype 1a because a transversion is required to create the variant 58S. For the NS5B inhibitors, the genetic barrier at positions conferring resistance was nearly identical in subtypes 1a and 1b, and single transitions or transversions were necessary in 5 positions to generate a drug-resistant variant of HCV. The positions C316Y and S556D required only one transition in all genotypes, Y448H and S556 G

  17. Epigenetic inheritance in apomictic dandelions

    NARCIS (Netherlands)

    Preite, V.

    2016-01-01

    Epigenetic variation, such as changes in DNA methylations, regulatory small RNAs (sRNAs) and chromatin modifications can be induced by environmental stress. There is increasing information that such induced epigenetic modifications can be transmitted to offspring, potentially mediating adaptive

  18. Epigenetic Mechanisms Underlie Genome Development

    Science.gov (United States)

    Lamm, Ehud

    2013-01-01

    Technological and methodological advances, in particular next-generation sequencing and chromatin profiling, has led to a deluge of data on epigenetic mechanisms and processes. Epigenetic regulation in the brain is no exception. In this commentary, Ehud Lamm writes that extending existing frameworks for thinking about psychological development to…

  19. Epigenetic inheritance, prions and evolution

    Indian Academy of Sciences (India)

    The field of epigenetics has grown explosively in the past two decades or so. As currently defined, epigenetics deals with heritable, metastable and usually reversible changes that do not involve alterations in DNA sequence, but alter the way that information encoded inDNAis utilized.The bulk of current research in ...

  20. Evolutionary significance of epigenetic variation

    NARCIS (Netherlands)

    Richards, C.L.; Verhoeven, K.J.F.; Bossdorf, O.; Wendel, J.F.; Greilhuber, J.; Dolezel, J.; Leitch, I.J.

    2012-01-01

    Several chapters in this volume demonstrate how epigenetic work at the molecular level over the last few decades has revolutionized our understanding of genome function and developmental biology. However, epigenetic processes not only further our understanding of variation and regulation at the

  1. Genetic horoscopes: is it all in the genes? Points for regulatory control of direct-to-consumer genetic testing

    NARCIS (Netherlands)

    Patch, C.; Sequeiros, J.; Cornel, M.C.

    2009-01-01

    The development of tests for genetic susceptibility to common complex diseases has raised concerns. These concerns relate to evaluation of the scientific and clinical validity and utility of the tests, quality assurance of laboratories and testing services, advice and protection for the consumer and

  2. Epigenetics and autism.

    Science.gov (United States)

    Mbadiwe, Tafari; Millis, Richard M

    2013-01-01

    This review identifies mechanisms for altering DNA-histone interactions of cell chromatin to upregulate or downregulate gene expression that could serve as epigenetic targets for therapeutic interventions in autism. DNA methyltransferases (DNMTs) can phosphorylate histone H3 at T6. Aided by protein kinase C β 1, the DNMT lysine-specific demethylase-1 prevents demethylation of H3 at K4. During androgen-receptor-(AR-) dependent gene activation, this sequence may produce AR-dependent gene overactivation which may partly explain the male predominance of autism. AR-dependent gene overactivation in conjunction with a DNMT mechanism for methylating oxytocin receptors could produce high arousal inputs to the amygdala resulting in aberrant socialization, a prime characteristic of autism. Dysregulation of histone methyltransferases and histone deacetylases (HDACs) associated with low activity of methyl CpG binding protein-2 at cytosine-guanine sites in genes may reduce the capacity for condensing chromatin and silencing genes in frontal cortex, a site characterized by decreased cortical interconnectivity in autistic subjects. HDAC1 inhibition can overactivate mRNA transcription, a putative mechanism for the increased number of cerebral cortical columns and local frontal cortex hyperactivity in autistic individuals. These epigenetic mechanisms underlying male predominance, aberrant social interaction, and low functioning frontal cortex may be novel targets for autism prevention and treatment strategies.

  3. Epigenetics and Autism

    Directory of Open Access Journals (Sweden)

    Tafari Mbadiwe

    2013-01-01

    Full Text Available This review identifies mechanisms for altering DNA-histone interactions of cell chromatin to upregulate or downregulate gene expression that could serve as epigenetic targets for therapeutic interventions in autism. DNA methyltransferases (DNMTs can phosphorylate histone H3 at T6. Aided by protein kinase Cβ1, the DNMT lysine-specific demethylase-1 prevents demethylation of H3 at K4. During androgen-receptor-(AR- dependent gene activation, this sequence may produce AR-dependent gene overactivation which may partly explain the male predominance of autism. AR-dependent gene overactivation in conjunction with a DNMT mechanism for methylating oxytocin receptors could produce high arousal inputs to the amygdala resulting in aberrant socialization, a prime characteristic of autism. Dysregulation of histone methyltransferases and histone deacetylases (HDACs associated with low activity of methyl CpG binding protein-2 at cytosine-guanine sites in genes may reduce the capacity for condensing chromatin and silencing genes in frontal cortex, a site characterized by decreased cortical interconnectivity in autistic subjects. HDAC1 inhibition can overactivate mRNA transcription, a putative mechanism for the increased number of cerebral cortical columns and local frontal cortex hyperactivity in autistic individuals. These epigenetic mechanisms underlying male predominance, aberrant social interaction, and low functioning frontal cortex may be novel targets for autism prevention and treatment strategies.

  4. The Role of Epigenetic Change in Autism Spectrum Disorders.

    Science.gov (United States)

    Loke, Yuk Jing; Hannan, Anthony John; Craig, Jeffrey Mark

    2015-01-01

    Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders characterized by problems with social communication, social interaction, and repetitive or restricted behaviors. ASD are comorbid with other disorders including attention deficit hyperactivity disorder, epilepsy, Rett syndrome, and Fragile X syndrome. Neither the genetic nor the environmental components have been characterized well enough to aid diagnosis or treatment of non-syndromic ASD. However, genome-wide association studies have amassed evidence suggesting involvement of hundreds of genes and a variety of associated genetic pathways. Recently, investigators have turned to epigenetics, a prime mediator of environmental effects on genomes and phenotype, to characterize changes in ASD that constitute a molecular level on top of DNA sequence. Though in their infancy, such studies have the potential to increase our understanding of the etiology of ASD and may assist in the development of biomarkers for its prediction, diagnosis, prognosis, and eventually in its prevention and intervention. This review focuses on the first few epigenome-wide association studies of ASD and discusses future directions.

  5. The role of epigenetic change in autism spectrum disorders

    Directory of Open Access Journals (Sweden)

    Yuk Jin eLoke

    2015-05-01

    Full Text Available Autism spectrum disorders (ASD are a heterogeneous group of neurodevelopmental disorders characterised by problems with social communication, social interaction and repetitive or restricted behaviours. ASD is comorbid with other disorders including attention deficit hyperactivity disorder, epilepsy, Rett syndrome and Fragile X syndrome. Neither the genetic nor the environmental components have been characterised well enough to aid diagnosis or treatment of non-syndromic ASD. However, genome-wide association studies have amassed evidence suggesting involvement of hundreds of genes and a variety of associated genetic pathways. Recently, investigators have turned to epigenetics, a prime mediator of environmental effects on genomes and phenotype, to characterise changes in ASD that constitute a molecular level on top of DNA sequence. Though in their infancy, such studies have the potential to increase our understanding of the aetiology of ASD and may assist in the development of biomarkers for its prediction, diagnosis, prognosis and eventually in its prevention and intervention. This review focuses on the first few epigenome-wide association studies of ASD and discusses future directions.

  6. Metastasis genetics, epigenetics, and the tumor microenvironment

    Science.gov (United States)

    KISS1 is a member of a family of genes known as metastasis suppressors, defined by their ability to block metastasis without blocking primary tumor development and growth. KISS1 re-expression in multiple metastatic cell lines of diverse cellular origin suppresses metastasis; yet, still allows comple...

  7. Genetics, Cytogenetics, and Epigenetics of Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Lucia Migliore

    2011-01-01

    Full Text Available Most of the colorectal cancer (CRC cases are sporadic, only 25% of the patients have a family history of the disease, and major genes causing syndromes predisposing to CRC only account for 5-6% of the total cases. The following subtypes can be recognized: MIN (microsatellite instability, CIN (chromosomal instability, and CIMP (CpG island methylator phenotype. CIN occurs in 80–85% of CRC. Chromosomal instability proceeds through two major mechanisms, missegregation that results in aneuploidy through the gain or loss of whole chromosomes, and unbalanced structural rearrangements that lead to the loss and/or gain of chromosomal regions. The loss of heterozygosity that occur in the first phases of the CRC cancerogenesis (in particular for the genes on 18q as well as the alteration of methylation pattern of multiple key genes can drive the development of colorectal cancer by facilitating the acquisition of multiple tumor-associated mutations and the instability phenotype.

  8. Molecular genetics and epigenetics of CACTA elements

    KAUST Repository

    Fedoroff, Nina V.

    2013-01-01

    The CACTA transposons, so named for a highly conserved motif at element ends, comprise one of the most abundant superfamilies of Class 2 (cut-and-paste) plant transposons. CACTA transposons characteristically include subterminal sequences of several

  9. An emerging role for epigenetic factors in relation to executive function.

    Science.gov (United States)

    Ibrahim, Omar; Sutherland, Heidi G; Haupt, Larisa M; Griffiths, Lyn R

    2017-11-20

    Executive function (EF) includes a range of decision-making and higher-order thinking processes. Although the genetic basis of EF has been studied and reviewed, epigenetic factors that influence EF are an emerging field of interest; here, we summarize the current research. Work relating to different word combinations of 'Executive Function' and 'Epigenetic' was identified through three academic search directories. Inclusion criteria were human populations, EF testing, epigenetic testing or genotyping related to epigenetic regulation. To date, 14 studies have been reported, which examined epigenetic variation, in particular DNA methylation, in relation to EF assessments conducted in human subjects, with some positive associations found. Study populations included healthy cohorts, as well as psychiatric and neurological patient cohorts. Epigenetics in relation to EF is an emerging area of investigation with relatively few studies to date. Most assay DNA methylation, with some studies suggesting that epigenetic factors can be associated with EF. EF constitutes complex phenotypic and genotypic correlates that differ because of cohort attributes as well as the targeted task examined. Larger studies are required to further elucidate the contribution of epigenetic factors to EF with the identification of epigenetic modifications influencing EF having potential to provide new biomarkers for neuropsychiatric disorders. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com

  10. Future clinical trials in DIPG: bringing epigenetics to the clinic

    Directory of Open Access Journals (Sweden)

    Andres E. Morales La Madrid

    2015-07-01

    Full Text Available In spite of major recent advances in DIPG molecular characterization, this body of knowledge has not yet translated into better treatments.To date,more than 250 clinical trials evaluating radiotherapy along with conventional cytotoxic chemotherapy as well as newer biologic agents,have failed to improve the dismal outcome when compared to palliative radiation alone.The biology of DIPG remained unknown until recently when the neurosurgical expertise along with the recognition by the scientific and clinical community of the importance of tissue sampling at diagnosis;ideally in the context of a clinical trial and by trained neurosurgical teams to maximize patient safety.These pre-treatment tumor samples,and others coming from tissue obtained post-mortem,have yielded new insights into DIPG molecular biology.We now know that DIPG comprises a heterogeneous disease with variable molecular phenotypes, different from adult high grade glioma,other non-pontine pediatric high grade gliomas and even between pontine gliomas.The discovery of histone H3.3 or H3.1 mutations has been an important step forward in understanding tumor formation,maintenance and progression.Pharmacologic reversal of DIPG histone demethylation therefore offers an important potential intervention strategy for the treatment of DIPG.To date,clinical trials of newly diagnosed or progressive DIPG with epigenetic modifiers have been unsuccessful.Whether this failure represents limited activity of the agents used,their CNS penetration,redundant pathways within the tumor,or the possibility that histone mutations are necessary only to initiate DIPGs but not maintain their growth,suggest that a great deal still needs to be elucidated in both the underlying biology of these pathways,and the drugs designed to target them.In this review, we discuss the role of both epigenetic and genetic mutations within DIPG and the development of treatment strategies directed against the unique abnormalities

  11. Direct-to-Consumer Genetic Testing and Personal Genomics Services: A Review of Recent Empirical Studies

    Science.gov (United States)

    Ostergren, Jenny

    2013-01-01

    Direct-to-consumer genetic testing (DTC-GT) has sparked much controversy and undergone dramatic changes in its brief history. Debates over appropriate health policies regarding DTC-GT would benefit from empirical research on its benefits, harms, and limitations. We review the recent literature (2011-present) and summarize findings across (1) content analyses of DTC-GT websites, (2) studies of consumer perspectives and experiences, and (3) surveys of relevant health care providers. Findings suggest that neither the health benefits envisioned by DTC-GT proponents (e.g., significant improvements in positive health behaviors) nor the worst fears expressed by its critics (e.g., catastrophic psychological distress and misunderstanding of test results, undue burden on the health care system) have materialized to date. However, research in this area is in its early stages and possesses numerous key limitations. We note needs for future studies to illuminate the impact of DTC-GT and thereby guide practice and policy regarding this rapidly evolving approach to personal genomics. PMID:24058877

  12. [Epigenetics' implication in autism spectrum disorders: A review].

    Science.gov (United States)

    Hamza, M; Halayem, S; Mrad, R; Bourgou, S; Charfi, F; Belhadj, A

    2017-08-01

    The etiology of autism spectrum disorders (ASD) is complex and multifactorial, and the roles of genetic and environmental factors in its emergence have been well documented. Current research tends to indicate that these two factors act in a synergistic manner. The processes underlying this interaction are still poorly known, but epigenetic modifications could be the mediator in the gene/environment interface. The epigenetic mechanisms have been implicated in susceptibility to stress and also in the pathogenesis of psychiatric disorders including depression and schizophrenia. Currently, several studies focus on the consideration of the etiological role of epigenetic regulation in ASD. The object of this review is to present a summary of current knowledge of an epigenetic hypothesis in ASD, outlining the recent findings in this field. Using Pubmed, we did a systematic review of the literature researching words such as: autism spectrum disorders, epigenetics, DNA methylation and histone modification. Epigenetic refers to the molecular process modulating gene expression without changes in the DNA sequence. The most studied epigenetic mechanisms are those that alter the chromatin structure including DNA methylation of cytosine residues in CpG dinucleotides and post-translational histone modifications. In ASD several arguments support the epigenetic hypothesis. In fact, there is a frequent association between ASD and genetic diseases whose epigenetic etiologies are recognized. A disturbance in the expression of genes involved in the epigenetic regulation has also been described in this disorder. Some studies have demonstrated changes in the DNA methylation of several autism candidate genes including the gene encoding the oxytocin receptor (OXTR), the RELN and the SHANK3 genes. Beyond the analysis of candidate genes, recent epigenome-wide association studies have investigated the methylation level of several other genes and showed hypomethylation of the whole DNA in brain

  13. DNA Methylation and Chromatin Remodeling: The Blueprint of Cancer Epigenetics

    Directory of Open Access Journals (Sweden)

    Dipanjan Bhattacharjee

    2016-01-01

    Full Text Available Epigenetics deals with the interactions between genes and the immediate cellular environment. These interactions go a long way in shaping up each and every person’s individuality. Further, reversibility of epigenetic interactions may offer a dynamic control over the expression of various critical genes. Thus, tweaking the epigenetic machinery may help cause or cure diseases, especially cancer. Therefore, cancer epigenetics, especially at a molecular level, needs to be scrutinised closely, as it could potentially serve as the future pharmaceutical goldmine against neoplastic diseases. However, in view of its rapidly enlarging scope of application, it has become difficult to keep abreast of scientific information coming out of various epigenetic studies directed against cancer. Using this review, we have attempted to shed light on two of the most important mechanisms implicated in cancer, that is, DNA (deoxyribonucleic acid methylation and histone modifications, and their place in cancer pathogenesis. Further, we have attempted to take stock of the new epigenetic drugs that have emerged onto the market as well as those in the pipeline that offer hope in mankind’s fight against cancer.

  14. The political implications of epigenetics.

    Science.gov (United States)

    Robison, Shea K

    2016-01-01

    Epigenetics, which is just beginning to attract public attention and policy discussion, challenges conventional understanding of gene-environment interaction and intergenerational inheritance and perhaps much more besides. Does epigenetics challenge modern political ideologies? I analyzed the narratives of obesity and epigenetics recently published in the more liberal New York Times and the more conservative Wall Street Journal. For the years 2010 through 2014, 50 articles on obesity and 29 articles on epigenetics were identified, and elements in their causal narratives were quantitatively analyzed using a well described narrative policy framework. The narratives on obesity aligned with the two newspapers' reputed ideologies. However, the narratives on epigenetics aligned with neither ideology but freely mixed liberal and conservative elements. This small study may serve as a starting point for broader studies of epigenetics as it comes to a