Textbook of Personalized Medicine - Second Edition [2015]

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do it and when to do it. The marks, which are not part of the DNA itself, can be
passed on from cell to cell as cells divide, and from one generation to the next.
Lifestyle and environmental factors can expose a person to chemical tags that
change the epigenome. The most characterized epigenetic modifi cations are DNA
methylation and histone modifi cation.
As part of its Roadmap for Medical Research, the NIH plans to develop a map of
the epigenomic marks that occur on the human genome. The progress can be fol-
lowed on the web site: http://commonfund.nih.gov/epigenomics. In addition to
genomics, knowledge of epigenomics is essential for understanding the pathogen-
esis of several diseases, particularly cancer, where a combination of alterations in
the genome as well as the epigenome promote the malignant transformation. The
combination of mutations, structural variations and epigenetic alterations differs
between each tumor, making individual diagnosis and treatment strategies neces-
sary for a personalized approach to management (Schweiger et al. 2013 ).


Genetics vs. Epigenetics


The sequence of the four nucleotides of the genetic code is compared to an indelible
ink that, with rare exceptions, is faithfully transcribed from cell to cell and from
generation to generation. The epigenetic code lies on top of this and is represented
by methyl groups added to the DNA base cytosine, as well as covalent changes in
histone proteins around which the DNA is coiled. This epigenetic information is
more like a code written in pencil in the margins around the DNA (Gosden and
Feinberg 2007 ). Regulation of gene expression by genetics involves a change in the
DNA sequence, whereas epigenetic regulation involves alteration in chromatin
structure and methylation of the promoter region. DNA methylation represents an
epigenetic means of inheritance without associated DNA sequence alterations. The
role of epigenetics in the etiology of human disease is increasingly recognized with
the most obvious evidence found for genes subject to genomic imprinting.


Cytomics as a Basis for Personalized Medicine


Cytomics is the structural and functional information is obtained by molecular cell
phenotype analysis of tissues, organs and organisms at the single cell level by image
or fl ow cytometry in combination with bioinformatic knowledge extraction con-
cerning nuclei acids, proteins and metabolites (cellular genomics, proteomics and
metabolomics) as well as cell function parameters like intracellular pH, transmem-
brane potentials or ion gradients. In addition, differential molecular cell phenotypes
between diseased and healthy cells provide molecular data patterns for (i) predictive
medicine by cytomics or for (ii) drug discovery purposes using reverse engineering
of the data patterns by biomedical cell systems biology. Molecular pathways can be


8 Non-genomic Factors in the Development of Personalized Medicine
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