Journal Article

Transgenerational genetic effects on phenotypic variation and disease risk

Joseph H. Nadeau

in Human Molecular Genetics

Volume 18, issue R2, pages R202-R210
Published in print October 2009 | ISSN: 0964-6906
Published online October 2009 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddp366
Transgenerational genetic effects on phenotypic variation and disease risk

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Traditionally, we understand that individual phenotypes result primarily from inherited genetic variants together with environmental exposures. However, many studies showed that a remarkable variety of factors including environmental agents, parental behaviors, maternal physiology, xenobiotics, nutritional supplements and others lead to epigenetic changes that can be transmitted to subsequent generations without continued exposure. Recent discoveries show transgenerational epistasis and transgenerational genetic effects where genetic factors in one generation affect phenotypes in subsequent generation without inheritance of the genetic variant in the parents. Together these discoveries implicate a key signaling pathway, chromatin remodeling, methylation, RNA editing and microRNA biology. This exceptional mode of inheritance complicates the search for disease genes and represents perhaps an adaptation to transmit useful gene expression profiles from one generation to the next. In this review, I present evidence for these transgenerational genetic effects, identify their common features, propose a heuristic model to guide the search for mechanisms, discuss the implications, and pose questions whose answers will begin to reveal the underlying mechanisms.

Journal Article.  6362 words.  Illustrated.

Subjects: Genetics and Genomics

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