Autistic Genetics

Some forms of autism seem to be linked with variations in certain genes, a new study says.

One of these chromosomes is not like the others (maybe).

The deletion of a certain cluster of 27 genes on the mammalian chromosome 16 – specifically a region known as 16p11.2 – causes autism-like features to develop in mouse brains. These mice exhibited hyperactivity, repetitive behaviors, and difficulty adjusting to new environments, much like human children with autism. (As I mention a lot on this blog, mouse brains provide pretty reliable models of certain human brain functions, which is why neuroscientists experiment on them.)

The idea that chromosome 16 might be linked to autism dates back to 2007, when Michael Wigler at Cold Spring Harbor Laboratory (CSHL) discovered that many children with autism had a deletion of a certain set of 27 genes in region 16p11.2.

Tired of acronyms yet? I sure hope not, because here come some more.

As the journal Proceedings of the National Academy of Sciences (PNAS) reports, a team led by Guy Horev at CSHL genetically engineered mice to manifest this same chromosomal copy number variation (CNV):

We used chromosome engineering to generate mice harboring deletion of the chromosomal region corresponding to 16p11.2, as well as mice harboring the reciprocal duplication. These 16p11.2 CNV models have dosage-dependent changes in gene expression, viability, brain architecture, and behavior. For each phenotype, the consequence of the deletion is more severe than that of the duplication.

In short, a deletion of those 27 genes produced autism-like symptoms, while mice with an extra copy of region 16p11.2 didn’t seem to be autistic at all.

Interestingly, half the mice with the deletion died soon after birth. The ones that survived to adulthood were physically healthy and fertile, but when the researchers studied their brains under MRI scans, they found a set of neurological symptoms that were all too recognizable:

[The mice] have alterations in the hypothalamus and exhibit a “behavior trap” phenotype—a specific behavior characteristic of rodents with lateral hypothalamic and nigrostriatal lesions.

The hypothalamus is a brain region involved in regulating our hormones, balancing our body temperature, and motivating us to perform semi-automatic tasks like eating, drinking, and sleeping. The nigrostriatal pathway connects the midbrain’s substantia nigra to the forebrain’s striatum; it’s a major dopamine pathway that’s involved in motivating movement. Abnormalities in all these regions have been linked with autism in previous studies.

The next step in this research will be to pinpoint which of the 27 genes in region 16p11.2 impact autistic development in what ways. The researchers hope future discoveries along those lines will help doctors diagnose autism early in a child’s life, or perhaps even predict its likelihood based on the genetics of the parents.

Like other predictive genetic tests, this could lead to some tough ethical dilemmas for would-be mothers and fathers – but it’s also likely to lead to more proactive treatments. And besides, even if you know your child will be born with autism, you never know if he or she might be the next Daniel Tammett or Temple Grandin.

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