Epigenetics, human imprintome, and chronic diseases.

Area of Science:

• Epigenetics
• Developmental Biology
• Genomics

Background:

• Two gene subsets, imprinted genes and metastable epialleles, link embryonic exposures to adult disease.
• Metastable epiallele gene expression (e.g., Agouti viable yellow (Avy) mice) is variable between individuals but tissue-uniform.
• Genomic imprinting, a parent-of-origin gene silencing mechanism, evolved in Therian mammals.

Purpose of the Study:

• To demonstrate how embryonic environmental exposures modify the epigenome and influence adult disease susceptibility.
• To highlight the role of imprinted genes and metastable epialleles in environmentally induced chronic diseases.
• To discuss the identification of human imprintome regions linked to chronic and behavioral disorders.

Main Methods:

• Utilized the Agouti viable yellow (Avy) mouse model to study epigenetic modifications.
• Investigated the effects of nutritional supplements, chemical toxicants, and low-dose ionizing radiation during embryogenesis.
• Employed the human imprintome array for identifying imprint control regions (ICRs) in peripheral samples.

Main Results:

• Confirmed that embryonic exposures alter adult disease susceptibility via epigenetic modification in the Avy mouse model.
• Established imprinted genes as functionally haploid disease susceptibility loci.
• Enabled identification of human imprintome ICRs associated with chronic diseases and behavioral disorders.

Conclusions:

• Metastable epialleles and imprinted genes are crucial in the etiology of environmentally induced human chronic diseases.
• Epigenetic regulation by imprinted genes and metastable epialleles provides a mechanism linking early environmental exposures to later-life health outcomes.
• The human imprintome array facilitates the identification of epigenetic biomarkers for disease risk.