Fishing for Genetic Links in Autism

This is the second installment in a 2-part series that addresses approaches to understanding the molecular underpinnings of autism. Learn more about "Brain Rules" here.

In my January column (“Fishing Expeditions and Autism: A Big Catch for Genetic Research?” Psychiatric Times, January 2009), I described the great difficulties researchers face characterizing the genetic basis of the disease. Complexities range from trying to establish a stable diagnostic profile to making sense of the few isolated mutations that show clear associations (either with disease or syndrome variants).

Using the metaphor of a fishing net, I discussed 2 overall research strategies that geneticists commonly use to catch these elusive sequences of interest. One strategy is to cast nets that act like large purse seiners to collect many sequences in a single (and usually quite expensive) effort. The other strategy is akin to dropping a single fishing line into the genetic waters to see if anything “bites.” In Part 1, I described one particularly successful strategy that snagged a large number of useful sequences.

Here, the focus narrows: I will not describe the isolation of many sequences, but rather only one. Our “catch” is called MeCP2, a gene whose mutations can give rise to a wide spectrum of related postnatal neurodevelopmental disorders—including autism spectrum disorders. I will start with some background regions about gene regulation, move to the biological functions of MeCP2, and then focus on studies in animal models that provide tantalizing hints about the origins of autistic behavior. My goal is to show that research progress in autism is a continuum of efforts, ranging from large projects with lots of identifiable sequences to small projects that focus on the properties of single genes.

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- Theory of Mind

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