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periods of starvation, it will turn into a

problem once food is again available in

abundance. Epigenetic should not be

confused with genes linked to the genetic

risk of developing diseases which are then

heritable (3). A better understanding to

what epigenetic is all about can be derived

from the Agouti mouse model (4). The

agouti gene in general with its alleles

determines hair colour. The Agouti mouse

has a yellow coat because of its special

agouti gene alleles. The animal is,

however, not only special in the colour of

its coat, but it is also fat and tends to develop cancer and

diabetes. The animals shown in the picture below are

genetically identical, approximately 1 year old females.

The phenotype differs in size and coat colour because of

the difference in the epigenome. The mother of the

animal on the left side was fed a normal mouse diet, but

the mother of the mouse on the right side received a diet

supplemented with methyl donors, i.e. choline, folic acid, betaine, and vitamin B12. Feeding a

pregnant female mouse with the methyl supplements changed the phenotype of the offspring in

that the offspring is of normal size and has a brown coloured coat (Figure 3).

The animal model nicely demonstrates an epigenetic effect in that the nutritional

environment changes the phenotype of the offspring. This phenomenon was originally described

as the interaction between genetics and environment (5). A more accurate definition refers to

gene functionality that is not encoded into the DNA sequence but can be hereditary (6). The

important issue is that the function of the gene is modified by environmental influences. A

definition, which is shorter, but less clear to those who not very familiar with genetics, refers to a

‘mitotically heritable alteration in gene expression potential’ (7).

Epigenetic modifications are attributed at present to three main mechanisms: these are

DNA methylation of the DNA base of cytosine, chromatin remodeling and micro-RNAs

modeling gene expression (8).

Basic genetics

To obtain a better understanding of what all this means it is necessary to recall some long

forgotten high school knowledge. It is useful to remember that nucleotides are letters of DNA

and RNA, that complimentary base pairs of DNA are formed through hydrogen bonds, that

guanine binds with cytosine, adenine with thymine and uracil instead of thymine as far as RNA

is concerned, that histones are small DNA binding proteins consisting mainly of lysine and

argentine and are the fundamental protein components of nucleosomes. The information of the

genetic code stored in the DNA is translated by RNA into protein. Transcription of RNA results

in mature RNA which is channeled out of the nucleus, and translation occurs at the ribosome

Fig.: 3 Agouti mouse and normal

offspring after special feeding

(Reproduced with the kind

permission by Dr. R. Jirtle

(

www.geneimprint.com)