Prospect of PGT for epigenetic inheritance

Abstract

Since long we know that genetic mutations are able to influence the expression of our genes. However, in the last 10-15 years it became evident that not only alterations in the genetic code but also other modifications are able to trigger changes in the RNA profile of a cell. The so called epigenetic modification can modify the DNA without changing the nucleotide sequence itself. These entirely new mechanisms can add or remove DNA methylation, induce histone modifications or use non-coding RNAs for induction of epigenetic programs. All these changes modulate expression of genes and thereby create a huge variability of expression patterns in the cells of a body. Even more interestingly, these epigenetic changes can be inherited via the germ-line and are thereby transmitted to the next generations. DNA methylation is believed to be the major epigenetic modifier especially in germ cells. Methylation patterns in somatic cells are normally stable. However, in germ cells there are two distinct time points where methylation patterns are changed or reprogrammed, a first one at the primordial germ cell stage, and a second one in the preimplantation embryo. After fertilization, the paternal genome is actively and the maternal genome is passively demethylated. During the first days of development different epigenetic marks are set in the newly established lineages in a blastocyst. Intrinsic and also extrinsic influences can disturb the reprogramming mechanism and may have an influence during further embryonic development, after birth or even later in life.