Well Being

On Autism Genetics

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Eye on DNA quotes Dr. David Levin in an article, The Genetic Journey in the Johns Hopkins Public Health Magazine feature:

The existing approaches and tools of genetic epidemiology work well to identify responsible factors when you’re dealing with diseases caused by a single mutation. They don’t work so well for complex diseases involving multiple genetic and environmental factors—some of the major public health problems in the U.S., like obesity, heart disease and Alzheimer’s [my emphasis]. To my mind, there’s a need for population-based and laboratory-based sciences to coalesce and develop new approaches to complex disease causation [my emphasis]. The first step is to train people in interdisciplinary ways so they understand the molecular sciences as well as epidemiology and biostatistics.

Dr. Levin's views on the need to consider interdisciplinary approaches to “complex disease causation” might also be applied in regard to theories of autism aetiology. Says Anthony Monaco, Director and Head of the Neurogenetics Group at the Wellcome Trust Centre, one of the leaders of the Autism Genome Project (AGP):

“The probability has always been that autism is highly genetic, but highly heterogeneous – that lots of different genes are involved. We now have a great chance of picking them up.”

Prof. Monaco is quoted in an August 27th article in the TimesOnline entitled Hunting the gene that traps children in their own world. While describing autism as “devastating” and, in its opeing paragraphs, as a “controversial and feared medical diagnosis” and a “cruel condition,” TimesOnline makes connections between new findings on autism and genetics published earlier this year. From these studies on genetics, it is suggested that autism may not be a single disorder

The first genetics study was conducted by the AGP and involved over 1,000 families. Entitled Mapping autism risk loci using genetic linkage and chromosonal rearrangements and appearing in Nature Genetics, the five-year study suggests that autism has “numerous genetic origins rather than a single or a few primary causes.” DNA samples from 1,168 families—”the largest cohort yet of ASD families yet assembled”—with two or more autistic children were analyzed.

The second genetics study was about spontaneous (de novo) mutations. 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. Wigler and his research found that 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). Notes the TimesOnline:

“Sporadic autism is the more common form of the disease and even the inherited form might derive from a mutation that occurred in a parent or grandparent,” the professor said.

If mutations of this sort are responsible, they would not show up in the AGP: they are new and unique to individuals and families, so will not surface from large comparisons of DNA.

Additional genetics research is cited to suggest that autism may not be a single disorder: Angelica Ronald, Francesca Happé and Robert Plomin, of the Institute of Psychiatry, have suggested that different sets of genes may influence each of the three criteria used to diagnose autism (social difficulties, communication difficulties, and behavior issues):

This has important implications for gene-hunting. It could be that genes have not been found because scientists have been treating autism as a whole. If different genes affect the communication and social elements of the disorder, finding them might involve looking at people who are not autistic, but who have mild versions of one of the problems. “We need to tackle whether we should look at autism as a single phenomenon, or whether it would be better to look, for example, just at autistic social problems,” Dr Ronald said.

Dr. Ronald also notes that learning more about the genetics of autism can help greatly in diagnosis and treatment. For myself, the more I learn about autism genetics, the more I see how Charlie is connected to Jim's and my families, and how very much he shares with all of us.