The completion of the human genome project in 2001 unraveled the genes with Mendelian inheritance and opened new issues related to multifactorial inheritance. Based on the tools of technology, Genome Wide Association Studies (GWAS) analyzed widely populations for predisposing genes. The results were impressive and they showed that there exists another type of regulation of the genome namely epigenome which results in more complex phenotypes. The epigenetic mechanisms including DNA methylation, changes in chromatin structure, imprinting, changes in protein confirmation and RNA-associated silencing are associated with the etiology and the complexity of phenotypes in multifactorial diseases. Moreover, they showed that the silenced part of the genome called heterochromatin is quite active. Heterochromatin consists from transposable elements (TEs) which are DNA sequences with the ability to move and integrate into the genome at different sites and control the function of neighboring genes. Their function is closely related to environmental influences. Reprogramming in germ lines is crucial to establish the totipotency of zygote, but epigenetic marks mainly with different methylation patterns across the genome control the activation and silencing of genes. Different evolutionary models have been proposed to explain the function of the epigenome in relation to disease.