Environmentally induced epigenetic transgenerational inheritance of sperm epimutations promote genetic mutations.

ABSTRACT: A variety of environmental factors have been shown to induce the epigenetic transgenerational inheritance of disease and phenotypic variation. This involves the germline transmission of epigenetic information between generations. Exposure specific transgenerational sperm epimutations have been previously observed. The current study was designed to investigate the potential role genetic mutations have in the process, using copy number variations (CNV). In the first (F1) generation following exposure, negligible CNV were identified; however, in the transgenerational F3 generation, a significant increase in CNV was observed in the sperm. The genome-wide locations of differential DNA methylation regions (epimutations) and genetic mutations (CNV) were investigated. Observations suggest the environmental induction of the epigenetic transgenerational inheritance of sperm epimutations promote genome instability, such that genetic CNV mutations are acquired in later generations. A combination of epigenetics and genetics is suggested to be involved in the transgenerational phenotypes. The ability of environmental factors to promote epigenetic inheritance that subsequently promotes genetic mutations is a significant advance in our understanding of how the environment impacts disease and evolution.

SUBMITTER: Skinner MK 

PROVIDER: S-EPMC4622673 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature