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Late fatherhood could increase the risk of autism

Late fatherhood increases the chance of babies being born with congenital disorders like autism and schizophrenia, according to an Icelandic study published recently in the journal Nature. But what exactly causes these conditions, and why does having children later in life increase the risks?

Genetic mutations and disorders

Late fatherhood could increase the risk of autism
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Spontaneous genetic mutations, or de novo mutations, are anomalies found in genes that aren't present in the gene pool passed on by the mother and father. These mutations take place in the egg or in the reproductive cells in the male and female bodies called gametes. Most of these genetic mutations have no adverse effect on child development and are actually essential to the process of evolution and diversification of the human gene pool. Some of them, however, have been linked to different neurological disorders like autism and schizophrenia.

Older fathers pass on twice as many genetic mutations

Icelandic neurologist Kari Stefansson and his team have compared full genome sequences of 78 couples with those of their children in order to identify any spontaneous mutations. They were able to establish that fathers were responsible for four times as many de novo mutations than mothers (55 compared with 14, on average). They also noticed that the number of de novo mutations increased with the father’s age, almost doubling between 20 and 36. 

When men become fathers at 30, 40 and older, the risk of their children developing disorders like autism, which are connected to these genetic mutations, is much higher. “The older men are when they become fathers, the higher the risk that mutations may occur when genes are passed down,” according to Stefansson. “As the number of mutations increases, it becomes more likely that one of them will lead to a disorder.” 

An increased risk

Autism is actually becoming increasingly common in developed countries. It's difficult to say exactly how many people suffer from autism, but the number is estimated at half a million in the UK. In the United States, the number of babies born with autism has increased sharply since 2007, to 1 in 88 births. Improved diagnosis of the condition may be a factor behind this increase in numbers, but it could also be down to an increased number of de novo mutations, according to Daniel Geschwind, a neurobiologist at the University of California in Los Angeles.

This isn’t the first time late fatherhood has been linked to autism. Two studies published this year* have identified dozens of new genetic mutations linked to autism. They have also produced evidence that these mutations are four times more likely to originate with the father’s genes.

To say men are solely responsible for passing on genes that can lead to autism is a step too far. In fact, while autism is hereditary, the majority of cases are not due to a single mutation. It is very likely that both parents transfer a genetic predisposition to their child, and the factors behind the genetic mutations that cause autism are still largely unknown.

Rate of de novo mutations and the importance of father's age to disease risk, Nature 488, 471-475, 23 August 2012 (summary online here).

1. De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Nature. 2012 Apr 4;485(7397):237-41 summary online).

2. Patterns and rates of exonic de novo mutations in autism spectrum disorders. Nature. 2012 Apr 4;485(7397):242-5 (summary online).



Posted 07.09.2012


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