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Transgenerational genetic effects on phenotypic variation and disease risk
1Department of Genetics, Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA. jhn4@case.edu
Human Molecular Genetics
|October 8, 2009
Summary
Beyond inherited genes and environment, epigenetic changes can transmit across generations. These transgenerational genetic effects, involving factors like chromatin remodeling, complicate disease gene discovery but may offer adaptive advantages.
Area of Science:
- Genetics
- Epigenetics
- Developmental Biology
Background:
- Phenotypes traditionally linked to inherited genetics and environment.
- Emerging evidence shows non-genetic factors induce heritable epigenetic changes.
- Transgenerational genetic effects influence offspring without direct genetic inheritance.
Purpose of the Study:
- Review evidence for transgenerational genetic effects.
- Identify common features and propose mechanistic models.
- Discuss implications for disease gene discovery and adaptation.
Main Methods:
- Literature review of epigenetic inheritance and transgenerational effects.
- Analysis of signaling pathways involved (chromatin remodeling, methylation, RNA editing, microRNAs).
- Development of a heuristic model for mechanistic investigation.
Main Results:
- Environmental factors, parental behaviors, and maternal physiology induce transgenerational epigenetic changes.
- Transgenerational epistasis and genetic effects demonstrate inheritance independent of genetic variants.
- Key molecular mechanisms include chromatin remodeling, DNA methylation, RNA editing, and microRNA activity.
Conclusions:
- Transgenerational genetic effects represent a significant departure from classical inheritance.
- Understanding these mechanisms is crucial for identifying disease genes.
- This mode of inheritance may be an adaptive strategy for transmitting beneficial gene expression profiles.
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