ABSTRACT
A gene can be rendered non-functional either by a spontaneously occurring mutation or by genetic engineering, often using gene knock-out models. A different class of genetic mutations which are causally associated with an obese phenotype involve disruption of signaling in the brain mediated by melanocortin type 4 receptors. Epigenetics refers to changes, sometimes heritable, in gene expression or phenotype caused by mechanisms other than alterations in the nucleotide sequence of deoxynucleic acid. One of the first demonstrations of epigenetic influence came from an examination of Dutch health records: Children who were born in 1940 during severe war-related famine, with inferred under-nutrition, had higher incidence of overweight or obesity in middle age as compared with children born without early life under-nutrition. Epigenetic mechanisms operate to modify the expression of the human genome over relatively short periods of time as well as, in some cases, transmission across generations.
