FAS is caused when women drink excessively during pregnancy. The alcohol damages the fetus, causing physical and behavioural changes that are evident after birth, such as growth retardation, changes to the shape and size of the skull, and central nervous system defects. Until now, little was known about the molecular mechanisms underlying the condition. Now it is apparent that 'epigenetic modifications' are at play - factors in the environment that cause permanent changes in gene expression, not to the DNA code itself but to the regulation of genes.
Researchers led by Dr Suyinn Chong, at the Queensland Institute of Medical Research, Australia, have developed a model that examines alcohol exposure in the mouse. They mated female mice that had two copies of the gene for yellow fur with males that had two copies of the gene for brown fur. This should yield predictable ratios of yellow and brown offspring. The pregnant females were fed alcohol during the first stages of pregnancy. The mice had blood alcohol levels of around 0.12 per cent - the equivalent in humans of around 1.5 times the legal driving limit in the UK.
When the offspring were born, the team observed a two-fold increase in the number of dark-furred animals compared to what was expected. Chong says that 'this means that the alcohol was affecting the 'epigenome' [epigenetic state] of the mice - controlling whether their genes were switched on or off'.
Some of the mice also had lower body weight and subtly malformed skulls compared to normal mice, features which are similar in the human FAS. Since fur colour is not relevant in humans, the team also looked at the mice's liver cells, finding 15 genes that were altered in the mice whose mothers drank alcohol during pregnancy. This further proves that epigenetic changes are caused by alcohol, and suggests that a similar mechanism could be at work in humans.
Humans with the syndrome have learning and memory problems that could lead to secondary problems such as mental health issues and trouble with the law. 'If we find specific genes have been affected by alcohol exposure, we could potentially screen newborns for the syndrome so that they can be offered social care early in life', says Chong, adding: 'But it is still early days'. She hopes that future work will define whether the epigenetic changes caused by alcohol are passed on through subsequent generations in the mice, and also examine behavioural changes.