Autism's Compelling Question: What is Causing Spontaneous Mutations Linked to Autism?

"One compelling question is what is causing the mutations ... The obvious conclusion one has to reach is that something environmental may well be the cause of these [spontaneous] changes in DNA"

Irva Hertz-Picciotto, autism researcher and professor of public health science at UC Davis, commenting on studies led by Matthew W. State and  Michael Wigler, showing hundreds of spontaneous mutations linked to autism, LA Times, June 9, 2011 

The gene environment interaction (GEI)  model of autism causation has been emerging over the past half dozen years. Even this humble layperson has noted the GEI model on several occasions on this blog. The "it's gotta be genetic" (IGBG) model was noted over a decade ago by Teresa Binstock. The GEI model has developed despite, or perhaps more accurately because of, the almost exclusive dedication of research dollars to  the  "it's gotta be genetic" (IGBG) model of autism causation. 

It is the failure of the pure genetic research to identify a specific genetic basis for  autism that only now is beginning to cause its adherents to doubt their faith.  It is the failure of the pure genetic model to explain autism causation beyond the existence of hundreds of spontaneous mutations that must finally make even the most determined of the IGBG school of autism causation ask ... could environmental factors be involved?  Spontaneous mutation is giving rise to spontaneous combustion as the purely genetic model of autism causation burns in the flames of failure.

Autism's most compelling question, as stated by Hertz-Picciotto: What is causing the spontaneous mutations?

Autism Gene Hunt

The last year has been filled with news of autism research breakthroughs coming at such a quickening pace that they are creating an Autism Knowledge Revolution. Much of the research has focussed on genetic contributions to autism with Professor Michael Wigler's spontaneous mutation theory commanding center stage. In Hunting the gene that traps children in their own world Times Online examines these breathtaking research developments in historical perspective and speculates on what we might expect in the next year as "gene chips" are applied to the databases of the Autism Genome Project:

The scientific success story of 2007 has been the coming of age of a new method of gene-hunting that can find the sort of genes with weak effects that are thought to influence autism. These genome-wide association studies compare the DNA of thousands of people who have a disease with healthy controls, using tools called “gene chips” to screen the entire human genome for hundreds of thousands of tiny genetic variations that differ between the two groups.

In recent months, the technique has revealed scores of genes that subtly influence common conditions such as diabetes, heart disease, breast cancer and multiple sclerosis, often raising the risk by as little as 10 per cent.

Autism is the next target. The Autism Genome Project (AGP), an international consortium that studies more than 1,000 families with at least two autistic members, is about to apply the tool to its database.

The TimesOnline article provides an excellent summary of the theory that autism actually consists of three separate developmental disorders which are most devestating when they all occur together:

What Professor Wigler’s theory does not account for is another aspect of new thinking about autism: that it may not be a single disorder, which if proven correct would certainly explain the spectrum element of autism disorders

For autism to be diagnosed, children must meet three criteria: they must show social impairment, communication difficulties and nonsocial problems such as repetitive and restricted behaviour. Yet there is an emerging consensus that these traits do not always go together and that there are people who meet the criteria for one or two characteristics but who do not receive any diagnosis. Autism, in short, may be the confluence of three separate developmental conditions. Only when they occur together is the result devastating.

Research by Angelica Ronald, Franc-esca Happé and Robert Plomin, of the Institute of Psychiatry, has suggested that each of these three problems is influenced by different sets of genes. The twin studies have shown that while each trait is highly heritable, they do not often overlap.

The multiple developmental disorders seems correct on an intuitive basis. It will be interesting to see if the studies provide evidence to support the theory.

Autism Researcher Dr. Michael Wigler - Who Is He?

The world of autism research is being rocked on an almost daily basis as the Autism Knowledge Revolution has wrested control of the world discourse on autism away from personal biases and opinions and placed it back in the ambit of solid scientific research. Dr. Michael Wigler and the Cold Spring Harbor Laboratory have been at the forefront of this explosion of autism research with their development of the genetic mutations explanation of autism. But who is Dr. Michael Wigler? Newsday provides an introduction and details his impressive background in mathematics and cancer research.

" Michael Wigler, the geneticist leading Cold Spring Harbor Laboratory's search for the genetic basis of autism, is a celebrated scientist who has made significant contributions to the molecular understanding of cancer.

Observers say it is his rare ability to see mathematical patterns in the complexities of genes that allow him to produce new ways of understanding disorders that underlie human debilities.

...

Having conducted research at the lab for 30 years, Wigler was in the forefront of scientists who developed the tools to probe cancer's DNA. He's also co-discoverer of the first human oncogene, a molecule capable of transforming normal cells into malignant ones. His work at the lab also led to the development of ROMA - representational oligonucleotide microarray analysis - a highly sensitive technique that allows scientists to profile the genetic basis of cancer and other diseases.

"Michael grew up as a mathematician and began to indulge in genomics," which required a strong mathematical background, said Dr. Mary-Claire King, the world-renowned medical geneticist at the University of Washington. She led the research team that discovered the breast cancer gene, BRCA1 and collaborated with Wigler on his initial work focusing on spontaneous mutations in autism.

Full Article at:

http://www.newsday.com/news/health/ny-hsside125331616aug14,0,6247673.story