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The influence of DNA sequence on epigenome-induced pathologies

Overview of attention for article published in Epigenetics & Chromatin, July 2012
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Title
The influence of DNA sequence on epigenome-induced pathologies
Published in
Epigenetics & Chromatin, July 2012
DOI 10.1186/1756-8935-5-11
Pubmed ID
Authors

Richard B Meagher, Kristofer J Müssar

Abstract

Clear cause-and-effect relationships are commonly established between genotype and the inherited risk of acquiring human and plant diseases and aberrant phenotypes. By contrast, few such cause-and-effect relationships are established linking a chromatin structure (that is, the epitype) with the transgenerational risk of acquiring a disease or abnormal phenotype. It is not entirely clear how epitypes are inherited from parent to offspring as populations evolve, even though epigenetics is proposed to be fundamental to evolution and the likelihood of acquiring many diseases. This article explores the hypothesis that, for transgenerationally inherited chromatin structures, "genotype predisposes epitype", and that epitype functions as a modifier of gene expression within the classical central dogma of molecular biology. Evidence for the causal contribution of genotype to inherited epitypes and epigenetic risk comes primarily from two different kinds of studies discussed herein. The first and direct method of research proceeds by the examination of the transgenerational inheritance of epitype and the penetrance of phenotype among genetically related individuals. The second approach identifies epitypes that are duplicated (as DNA sequences are duplicated) and evolutionarily conserved among repeated patterns in the DNA sequence. The body of this article summarizes particularly robust examples of these studies from humans, mice, Arabidopsis, and other organisms. The bulk of the data from both areas of research support the hypothesis that genotypes predispose the likelihood of displaying various epitypes, but for only a few classes of epitype. This analysis suggests that renewed efforts are needed in identifying polymorphic DNA sequences that determine variable nucleosome positioning and DNA methylation as the primary cause of inherited epigenome-induced pathologies. By contrast, there is very little evidence that DNA sequence directly determines the inherited positioning of numerous and diverse post-translational modifications of histone side chains within nucleosomes. We discuss the medical and scientific implications of these observations on future research and on the development of solutions to epigenetically induced disorders.

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Mendeley readers

The data shown below were compiled from readership statistics for 52 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 2%
Greece 1 2%
Argentina 1 2%
Unknown 49 94%

Demographic breakdown

Readers by professional status Count As %
Researcher 14 27%
Student > Ph. D. Student 9 17%
Professor > Associate Professor 6 12%
Student > Master 6 12%
Student > Bachelor 5 10%
Other 10 19%
Unknown 2 4%
Readers by discipline Count As %
Agricultural and Biological Sciences 35 67%
Biochemistry, Genetics and Molecular Biology 4 8%
Medicine and Dentistry 4 8%
Pharmacology, Toxicology and Pharmaceutical Science 1 2%
Social Sciences 1 2%
Other 3 6%
Unknown 4 8%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 21 July 2012.
All research outputs
#9,958,546
of 12,440,173 outputs
Outputs from Epigenetics & Chromatin
#316
of 358 outputs
Outputs of similar age
#85,447
of 119,886 outputs
Outputs of similar age from Epigenetics & Chromatin
#1
of 1 outputs
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So far Altmetric has tracked 358 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.6. This one is in the 6th percentile – i.e., 6% of its peers scored the same or lower than it.
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