Four new studies this week take on the genetics of autism, finding further evidence that older fathers are at increased risk of having an autistic child and suggesting that, overall, the genetic roots of the condition are incredibly complex.
Three of the studies, which were published in Nature, looked at new, or de novo, genetic mutations, which are not inherited but occur spontaneously around conception, in autistic children without any affected siblings.The researchers compared these children to each other and in some cases, also to their parents, and found changes in six candidate genes, three of which hadnt previously been linked to autism.
The basic finding is that new mutations present in sex cells carry substantial risk for autism, says Dr. Matthew State, a professor of psychiatry at Yale, who led one of the studies.
States study found that 15% of autism cases in families with no other autistic children were linked to de novo mutations in either the sperm or the egg that joined during conception. The three studies overall confirmed prior research suggesting that older fathers sperm is more likely to carry these mutations. In one study, researchers at the University of Washington in Seattle found that the mutations were four times more likely to occur in the fathers than in the mothers and the risk for men began increasing at age 35.
That may be because the older men are, the more times their sperm-creating cells have copied themselves, and each time a cell is copied, there is a chance that a mutation will occur. Previous studies have found that men over 50 have double the risk of having an autistic child, compared with those under 30, and the odds are four times greater for those over 55.
(MORE: Researcher Simon Baron-Cohen: Autisms Lone Wolf)
In another of the Nature studies, Harvard researchers found that de novo mutations were slightly higher among autistic people than those in the general population. The findings may help explain the recent rise in autism a government study last week put the rate of autism at 1 in 88 U.S. children which has occurred too quickly to be explained by the spread of hereditary genes. While more than half of the risk of autism is believed to be inherited studies find, for example, that 60% to 90% of identical twins are both autistic, sometimes to differing degrees in at least 70% of cases of autism, a known underlying genetic cause cant be identified.
The researchers focused on mutations that were most likely to interfere with gene function not those that most people acquire but are harmless thereby narrowing their search to those rare mutations that may occur only in autistic people. Then, they narrowed things further by looking at genes that had at least two such mutations. The odds that two or more mutations that cause serious problems with protein-making in the same gene also occur by chance in autism are infinitesimal.
These are like lightning strikes in the genome, State says, noting that the technique researchers used to find them should allow them to home in on genes that are genuinely important in the disorder. We are [now] able to determine what the threshold should be for calling something an autism gene.
Now we have real path forward, State says, explaining that as you start to accumulate these individual genes that you know are related, that opens the door to understanding the biology. Once you know the gene, you can examine the protein it makes. Then, even in people who dont have the damaged gene, adding that protein may help because a deficit in that protein might result in their autism via a different pathway.
Go here to read the rest:
Autism Studies Confirm Genetic Complexity and Risk for Older Fathers
Recommendation and review posted by G. Smith
