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'Selfish' tumor cells point to link between older fathers and genetic diseases

2 November 2009
Appeared in BioNews 532

Researchers from the University of Oxford and Copenhagen University Hospital have discovered a surprising link between the development of rare but benign testicular tumours and the genetic transmission of certain genetic diseases, such as achondroplasia (commonly known as dwarfism), Apert, Noonan and Costello syndromes, as well as some conditions causing stillbirth. The study, funded by the Wellcome Trust and the Danish Cancer Society, and published in the journal Nature Genetics, could help explain the origin of several serious conditions affecting children, and may be a stepping stone towards understanding why common diseases including breast cancer, autism and schizophrenia, seem to be more frequent in the offspring of older fathers.

Spermatocytic seminomas, a form of rare testicular tumour, are caused by genetic mutations in testicular cells and affect about one in 100,000 men. Both the cell mutations and tumours are usually harmless to the men, but the researchers believe they can change the germ cells that create sperm, allowing mutations to be passed on in the DNA of their children. The mutations help the tumour cells to divide, but when transmitted to the offspring they can cause abnormal growth. As men get older, tiny clumps of mutant cells accumulate, and because the same cells also produce sperm, the numbers of sperm carrying the mutations also increase. This raises the risk to older fathers of having affected children.

Professor Andrew Wilkie, of the University of Oxford, who led the research, explained that the discovery of such 'selfish' mutations that benefit the germ cell but not the offspring, may simply be 'the tip of a large iceberg of mildly harmful mutations being introduced into our genome.' He went on to say that while the mutations would be 'too weak and too rare to be picked up by our current technology... their sheer number would have a cumulative effect, leading to disease.'

The research dispels the notion that women are the only ones who need to be concerned with having children later in life and complements other research over the last decade that has shown how the quality of a man's sperm deteriorates with age. One previous study in Israel found a six fold risk of having a child with autism for men over 40 compared with men under 30, and another found an increased risk of 3.6 percent for every additional five years.

However, while the risk of passing on rare genetic disorders to children is almost tenfold higher for men over 50 compared to those in their 20s, the risk is still relatively low. According to Professor Wilkie, 'the total additional risk is still only a fraction of 1 per cent.'

Older fathers linked to genetic disease due to testicular tumours
The Daily Telegraph |  26 October 2009
Revealed: why children of older men are more likely to have health problems
The Independent |  26 October 2009
Scientists discover link between older dads and genetic diseases
The Times |  26 October 2009
Testicular Tumors May Explain Why Some Diseases Are More Common In Children Of Older Fathers
Science Daily |  26 October 2009
Why older fathers are more likely to have children with genetic disorders
The Daily Mail |  26 October 2009
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