Social circumstances often impinge on later generations in a socio-economic manner, giving children an uneven start in life. Overfeeding and overeating might not be an exception. The pathways might be complex but one direct mechanism could be genomic imprinting and loss of imprinting. An intergenerational "feedforward" control loop has been proposed, that links grandparental nutrition with the grandchild's growth. The mechanism has been speculated to be a specific response, e.g. to their nutritional state, directly modifying the setting of the gametic (...) imprint on one or more genes. This study raises the question: Can overnutrition during a child's slow growth period trigger such direct mechanisms and partly determine mortality?Data were collected by following-up a cohort born in 1905 in Överkalix parish, northernmost Sweden. The probands were characterised by their parents' or grandparents' access to food during their own slow growth period. Availability of food in the area was defined by referring to historical data on harvests and food prices, records of local community meetings and general historical facts.If there was a surfeit of food in the environment when the paternal grandfather was a 9–12 year old boy a shortening of the proband survival could be demonstrated. The influence of parents', maternal grandparents' and paternal grandmothers' access to food during their slow growth period was discounted in a multivariable analysis. The results are indicative of very early programming mechanisms in human adaptation to the social environment. (shrink)

In contrast to the biallelic expression of most genes, expression of genes subject to genomic imprinting is monoallelic and based on the sex of the transmitting parent. Possession of only a single active allele can lead to deleterious health consequences in humans. Aberrant expression of imprinted genes, through either genetic or epigenetic alterations, can result in developmental failures, neurodevelopmental and neurobehavioral disorders and cancer. The evolutionary emergence of imprinting occurred in a common ancestor to viviparous mammals after divergence from the (...) egg‐laying monotremes. Current evidence indicates that imprinting regulation in metatherian mammals differs from that in eutherian mammals. This suggests that imprinting mechanisms are evolving from those that were established 150 million years ago. Therefore, comparing genomic sequence of imprinted domains from marsupials and eutherians with those of orthologous regions in monotremes offers a potentially powerful bioinformatics approach for identifying novel imprinted genes and their regulatory elements. Such comparative studies will also further our understanding of the molecular evolution and phylogenetic distribution of imprinted genes. BioEssays 25:577–588, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

The contribution of inherited non‐genetic factors to complex diseases is of great current interest. The ways in which mothers and fathers can affect their offspring's health clearly differ as a result of the intimate interactions between mother and offspring during pre‐ and postnatal life. There is, however, potential for some overlap in mechanisms, particularly epigenetic mechanisms. A small number of epidemiological studies and animal models have investigated the non‐genetic contribution of the parents to offspring health. Discovering new mechanisms of disease (...) inheritance is technically difficult, especially in genetically, socially and environmentally heterogeneous human populations. Therefore, rigorous experimental design, appropriate sample numbers and the use of high‐throughput technologies are necessary to provide convincing evidence. Based on recent examples from the literature, here we propose several ways to improve human studies that aim to identify the underlying mechanisms of transgenerational inheritance of metabolic disease. (shrink)