Imprinted genes as potential genetic and epigenetic toxicologic targets.

Murphy, Susan K.; Jirtle, Randy L.

doi:10.1289/ehp.00108s15

Cited by 27 publications

(18 citation statements)

References 167 publications

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“…Imprinted loci are now known to be susceptible for inducing neurobehavioral disorders and developmental disorders (reviewed by Murphy & Jirtle, 2000). In terms of adult disease, however, so far imprinting has been mainly studied in terms of cancer.…”

Section: Imprints and Adult Disease -Is There A Link?mentioning

confidence: 99%

“…As many imprinted loci have either tumour suppressor function or protooncogenic potential, both mutations and epimutations are commonly detected in a variety of tumours (reviewed by Murphy & Jirtle, 2000). For example, the IGF2R locus is inactivated in a variety of human tumours.…”

Section: Imprints and Adult Disease -Is There A Link?mentioning

confidence: 99%

“…Although the gene is imprinted in post-implantation tissues of the mouse, it's imprinting in human is polymorphic, with only a minority of people showing monoallelic, maternal expression. However, since over 50% of patients with Wilm's tumour of the kidney exhibit at least partial imprinting of IGF2R (Xu et al, 1997), these patients may exhibit increased vulnerability as only one 'hit' rather than two may be needed for oncogenesis (Murphy & Jirtle, 2000). This may illustrate a wider mechanism for disease susceptibility as a consequence of disrupted imprinting.…”

Section: Imprints and Adult Disease -Is There A Link?mentioning

confidence: 99%

“…the role of Igf2r in effecting placental neovascularisation (see Young & Fairburn, 2000). Altered levels of this and other IGF-related genes (such as Gpc3, Grb10 etc) may furthermore affect fetal growth by influencing expression of other members of the IGF-related growth axis, including levels of Igf2 and Igfbps (Murphy & Jirtle, 2000;Young & Fairburn, 2000).…”

Section: Direct Disruptions In Imprinted Genesmentioning

confidence: 99%

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Imprinting of Genes and the Barker Hypothesis

Young¹

2001

twin res

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Section: Imprints and Adult Disease -Is There A Link?mentioning

confidence: 99%

Section: Imprints and Adult Disease -Is There A Link?mentioning

confidence: 99%

Section: Imprints and Adult Disease -Is There A Link?mentioning

confidence: 99%

Section: Direct Disruptions In Imprinted Genesmentioning

confidence: 99%

See 2 more Smart Citations

Imprinting of Genes and the Barker Hypothesis

Young¹

2001

twin res

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“…Most are unmethylated (in which occur near the transcription start sites) under normal circumstances except those associated with imprinted genes, genes subjected to X-chromosome inactivation, and transposable elements [31,32,35,36]. In this regard, DNA methylation is thought to repress inappropriate expression of endogenous transposons that may disrupt the genome and are involved in parental-specific silencing of one allele of imprinted genes [31,35,37]. In addition, about 70% of CGIs are associated with DNA sequences 200 bp to 2 kb long located in the promoter, the first and second exons, and the first intron regions of all genes (5′ CGIs), suggesting that CGIs are important for gene regulation [31,35,36].…”

mentioning

confidence: 99%

Epigenetic reprogramming and imprinting in origins of disease

Tang

2007

Rev Endocr Metab Disord

217

134

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The traditional view that gene and environment interactions control disease susceptibility can now be expanded to include epigenetic reprogramming as a key determinant of origins of human disease. Currently, epigenetics is defined as heritable changes in gene expression that do not alter DNA sequence but are mitotically and trans-generationally inheritable. Epigenetic reprogramming is the process by which an organism's genotype interacts with the environment to produce its phenotype and provides a framework for explaining individual variations and the uniqueness of cells, tissues, or organs despite identical genetic information. The main epigenetic mediators are histone modification, DNA methylation, and non-coding RNAs. They regulate crucial cellular functions such as genome stability, X-chromosome inactivation, gene imprinting, and reprogramming of non-imprinting genes, and work on developmental plasticity such that exposures to endogenous or exogenous factors during critical periods permanently alter the structure or function of specific organ systems. Developmental epigenetics is believed to establish "adaptive" phenotypes to meet the demands of the later-life environment. Resulting phenotypes that match predicted later-life demands will promote health, while a high degree of mismatch will impede adaptability to later-life challenges and elevate disease risk. The rapid introduction of synthetic chemicals, medical interventions, environmental pollutants, and lifestyle choices, may result in conflict with the programmed adaptive changes made during early development, and explain the alarming increases in some diseases. The recent identification of a significant number of epigenetically regulated genes in various model systems has prepared the field to take on the challenge of characterizing distinct epigenomes related to various diseases. Improvements in human health could then be redirected from curative care to personalized, preventive medicine based, in part, on epigenetic markings etched in the "margins" of one's genetic make-up. NIH Public Access Author ManuscriptRev Endocr Metab Disord. Author manuscript; available in PMC 2014 June 13. Epigenetics meets genetics in disease susceptibilityIn the past, susceptibility of disease was believed to be determined solely by inheritable information carried on the primary sequence of the DNA. Individuals are endowed with different genotypes that dictate how they respond to endogenous factors such as development cues, hormones, and cytokines or to exogenous influences, including nutrient availability, infection, physical activities, social behavior, and other environmental factors. Over time, these responses form the basis of genetic variability to disease susceptibility. Aberrant changes in linear DNA sequence result in mutations, deletions, gene fusion, tandem duplications, or gene amplifications causing dysregulation of gene expression that underlies the genesis of disease [1][2][3][4][5][6][7]. Recently, however, it has become clear that epigenetic disr...

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