Spontaneous gene mutations may account for half of all cases of autism in males: By now you’ve probably heard about this finding, and about a new model of autism genetics published in Proceedings of the National Academy of Sciences. For a cogent overview, see John Timmer’s July 24th post on Ars Technica. The title of the post, Autism may all be in the genes contains a hidden polemic: Most people take the view that a person has a “genetic predisposition to autism which is “triggered by environmental factors” and shy away from saying that autism is wholly genetic.
Timmer notes that
“genetics can accurately model much of the incidence of autism if you make some very specific assumptions about modes of inheritance”—assumptions which are based on “suggested by what’s already known about the disease.”
Under geneticist Michael Wigler of Cold Spring Harbor Laboratory in Long Island, NY, researchers studied families who have two or more autistic children and considered what the chances were for families whose first two children were autistic to have a third autistic child. In 86 families with two autistic children and with a third, male child, 42 of the third-born children had autistic symptoms. Notes the July 24th Nature.com:
This suggests that parents had a one-in-two chance of passing on a mutation to their offspring, matching a dominant inheritance pattern……
Using mathematical models, Wigler’s team found that the simplest way to describe the patterns of autism inheritance was to divide parents into two risk classes: those who carry a pre-existing autism-causing mutation, and those who do not.
The models suggest that about half of autistic children are born to parents with no previous genetic predisposition to autism, suggesting that the cases are caused by spontaneous mutations.
According to Wigler and his research team, mothers spontaneously acquire genetic mutations that are specific for autism. While the mothers themselves do not have autism, there is a 50% chance that they will transit the autism-related mutations to their children. There are, therefore, families who are at a “low risk” to have an autistic child, and families who are “high risk” (in which the mother carries the mutations but does not show autistic symptoms).
The team determined that most cases of autism arise from novel, spontaneous mutations passed down from one or both parents, resulting in large gaps in a person’s genome often encompassing several genes, which are then disrupted or inactivated. (This loss of genetic code—known as copy number variation—results in an offspring receiving only one of the standard two copies of a gene, which could cause an insufficient amount of protein to be produced by those genes.) In most instances, this mutation will result in an autistic child. However, in some cases—more likely in girls than boys—the recipient of this mutation will not produce any symptoms.
“When that child matures and becomes a parent, they have a 50 percent chance of transmitting … [their mutation] … to a child that might not be as lucky as they were, especially if … [its] … a boy,” Wigler says. “So, they will be transmitting this with close to a 50 percent frequency—and that is the source of the high-risk families.”
Some might respond to these findings by saying that mercury or some environmental toxin created the genetic mutations. My response—my very personal, autism-mother-on-her-soapbox response—is to ask: Ok, spontaneous genetic mutations——–so, are we—-am I—-in the “high risk” 50%?
I am going to posit that I am. As I review my extended family, many members of which are engineers or work in computers or write software or are in IT—some members of which could be placed on some spectrum of quirky geekitude0000I find it perhaps notable that I (who have always written and loved poetry, and don’t do math), have an autistic child (and very happily so, after yet another afternoon passed at the swimming pool praising Charlie for not minding too much that the water slide was closed, an ABA session during which he kept running straightways out the garage door and struggled to say the /ch/ in his own name, and trying to show him how to push the shopping cart s-l-o-w-l-y and not into other shoppers). Some have suggested that there is a sort of “autism cluster” in Silicon Valley; the Valley is where many of my cousins live and work, while here I have been away on the East Coast teaching Latin and Greek and the Classics and teaching college students how to write a good essay.
Maybe those autism genes skipped around and settled in me, who find more and more of Charlie in me and of me in Charlie with each passing day.
Mutatis mutandis goes the Latin: That which has been changed, had to be changed. There can be no doubt that my life has been profoundly changed and shaped by the experience of raising Charlie—-the change of a lifetime that I am grateful for. But what new and difficult choices might parents face if they are told that they are at “high risk” to have a child like him? What changes might happen in our world and among us human beings?