Passing it on: genetic clues to what runs in the family

Jonathan Leake      According to a new science, known as epigenetics, your ancestors’ diet, smoking habits, exposure to pollutants and levels of obesity could be affecting you today. In turn, your lifestyle could affect your children and grandchildren. For millions of people choosing to delay parenthood this raises new moral questions.    Some of the answers may be emerging. There is, for example, evidence that the recent surge in diseases such as diabetes, obesity and heart disease is partly linked to the lifestyles of past generations.    Last week academics at Baylor College of Medicine in Houston, Texas, published research showing that overweight mothers produce offspring who become even heavier, resulting in the spread of obesity across the generations. “There is a worldwide obesity epidemic,” said Robert Waterland, a professor of paediatrics who led the study. “Why is everyone getting heavier and heavier? One hypothesis is that maternal obesity before and during pregnancy causes epigenetic changes in the ways genes are expressed.”    Marcus Pembrey of the Institute of Child Health at University College London identified 166 fathers who admitted smoking before they were aged 11, and whose sons had a sharply elevated risk of obesity. The implication was that smoking had altered the way their genes worked without actually changing the genes.    Steve Jones, professor of genetics at University College London, said: “The evidence is increasingly that environmental factors like diet or stress can affect organisms in ways that are transmitted to offspring without any changes to DNA.”    Such apparent conflicts can be resolved but only by finding out what is happening at the level of DNA molecules, and scientists have never had that power until now. “The technologies for epigenetics arose from the human genome project and have only become widely available within the last few years,” said Stephan Beck, professor of medical genomics at the Cancer Institute, University College London. “That is what makes it so exciting.”    A key finding is that although DNA molecules control almost everything that happens in a cell, each molecule contains far more information than any single cell needs. A liver cell, for example, has no need for the genes that govern sperm production, while a brain cell that started generating, say, hair or nails could be positively dangerous. This means that in every cell some genes are turned on but many more are “trussed up” and neutralised by a host of smaller molecules. The change, then, is not to the DNA itself but to the “switches” that turn the genes on or off.    The system that oversees this process, the epigenome, is meant to be flexible enough for such genes to be brought in and out of play as needed. Sometimes, however, it goes wrong.    “The brain is particularly susceptible to epigenetic changes, especially during development,” said Dr Jonathan Mill, a lecturer in psychiatric epigenetics at the Institute of Psychiatry. “That is why pre-natal exposure to alcohol or other toxins may have such a strong effect.”    For humans perhaps the most important finding of epigenetics is that we are not owners of our genes but their guardian. If we drink heavily, take drugs, get fat or wait too long to reproduce, then epigenetics might start tying up some of the wrong genes and loosening the bonds on others. Sometimes those changes will affect sperm and egg cells.    One of the clearest pieces of evidence for such changes emerged from the work of Avi Reichenberg, also of the Institute of Psychiatry. He found children born to fathers aged 40-plus were almost six times more likely to have autism than those born to fathers under 30 and that the effect appeared to be epigenetic. In a society where people have children later in life, such effects have huge medical and social implications, suggesting that people putting off parenthood should be looking after their DNA. SUNDAY TIMES, LONDON