Non‐genomic transgenerational inheritance of disease risk

Abstract

That there is a heritable or familial component of susceptibility to chronic non-communicable diseases such as type 2 diabetes, obesity and cardiovascular disease is well established, but there is increasing evidence that some elements of such heritability are transmitted non-genomically and that the processes whereby environmental influences act during early development to shape disease risk in later life can have effects beyond a single generation. Such heritability may operate through epigenetic mechanisms involving regulation of either imprinted or non-imprinted genes but also through broader mechanisms related to parental physiology or behaviour. We review evidence and potential mechanisms for non-genomic transgenerational inheritance of 'lifestyle' disease and propose that the 'developmental origins of disease' phenomenon is a maladaptive consequence of an ancestral mechanism of developmental plasticity that may have had adaptive value in the evolution of generalist species such as Homo sapiens.

Transgenerational Epigenetic Inheritance: Prevalence, Mechanisms, and Implications for the Study of Heredity and Evolution

“…The offspring's response could be interpreted as a misfired predictive response-the consequences of a strategy that evolved when the parents' and the offspring's conditions matched. The effects of such mismatches and their medical significance have been discussed by Gluckman and Hanson (2005;Gluckman et al 2007).…”

“…Baylin and Jones (2007) review the epigenetics of cancer, and Zoghbi and Beaudet (2007) review diseases caused by defects in chromatin marking and imprinting. The epigenetic aspects of metabolic diseases and their transgenerational effects are also being intensely studied (see Bateson et al 2004;Gluckman and Hanson 2005;Gluckman et al 2007;Petronis 2004Petronis , 2006. The epidemiological aspects of epigenetic inheritance were reviewed by Jablonka (2004b), and the importance of epigenetics for aging research has been discussed by Vanyushin (1973), Holliday (1984), Lamb (1994), and Issa (2000).…”

Sexual dimorphism in environmental epigenetic programming

“…Epidemiological data and case studies suggesting or demonstrating the existence of TGEs with sexual dimorphism are also available for humans [82][83][84][85][86]. Undeniably, epigenetic processes provide the most plausible explanation for these observations, but the involvement of such processes in human developmental programming or in any epidemiological instance of transmission to subsequent generations has yet to be demonstrated.…”

Epigenetic regulation in obesity

“…2 Epigenetics was originally defined as 'heritable changes that regulate gene expression that occur without a change in the nucleotide sequence' (for review, see Bird 3 ), and recently defined as 'any long-term change in gene function that persists even when the initial trigger is long gone that does not involve a change in gene sequence or structure'. 4 Epigenetic modifications can be passed from one cell generation to the next (mitotic inheritance) and may be passed between generations (meiotic inheritance) 5,6 (for review, see Gluckman et al 7 ), although the evidence of true transgenerational epigenetic inheritance (that is, to the F3 generation since primordial germ cells (becoming F2) of the offspring (F1) may be affected in utero of F0) is limited in mammals because of robust prenatal genome-wide epigenetic reprogramming. The dynamics of epigenetics make it possible to respond reversibly to environmental cues, but also to firmly cement cell-type-specific gene programs.…”