The emerging science of epigenomics
Human Molecular GeneticsPublished 15 April 2006
Pauline A. Callinan, Andrew P. Feinberg
Citations314
SJR quartileQ1
SJR score1.56
SNIP0.92
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TL;DR
A number of new epigenomic strategies are emerging to exploit microarray formats with varying substrate choice, pre-processing and data analysis designed to detect large numbers of variations in DNA methylation and chromatin modification.
Abstract
One of the most exciting frontiers in both epigenetics and genome sciences is the new field of epigenomics. This new discipline promises novel insights into the genome because of its potential to detect quantitative alterations, multiplex modifications and regulatory sequences outside of genes. A number of new epigenomic strategies are emerging to exploit microarray formats with varying substrate choice, pre-processing and data analysis. These approaches are designed to detect large numbers of variations in DNA methylation and chromatin modification. Many groups are joining forces toward developing an organized Human Epigenome Project to exploit these new technologies to better understand the basis of normal development and human disease.
Keywords
Biochemistry, Genetics and Molecular Biology
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The extent of karyotypic instability and hypomethylation shows some correlation with the stage of tumour progression, and these changes may be important in generating the phenotypic diversity which allows the selection of variants during neoplasia and metastasis.
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