A Tale of Two Studies – Part the Second
We now return to our previous story…
Strong Association of De Novo Copy Number Mutations with Autism.
Sebat J, Lakshmi B, Malhotra D, Troge J, Lese-Martin C, Walsh T, Yamrom B, Yamrom B, Yoon S, Krasnitz A, Kendall J, Leotta A, Pai D, Zhang R, Lee YH, Hicks J, Spence SJ, Lee AT, Puura K, Lehtimaki T, Ledbetter D, Gregersen PK, Bregman J, Sutcliffe JS, Jobanputra V, Chung W, Warburton D, King MC, Skuse D, Geschwind DH, Gilliam TC, Ye K, Wigler M.
Science. 2007 Mar 15; [Epub ahead of print]
In this study, the authors used ROMA, a type of comparative genome hybridization, to look for de novo mutations in autistic children. They looked at 195 autistic children and their parents (need to look at the parents’ genome to know if the mutation was inherited or arose spontaneously) and 196 unaffected children and their parents.
What they found was – to put it mildly – very interesting.
The size of the human genome limited the resolution of the technique (in this study) such that they could detect only about 15% of the mutations that cytogenetic techniques indicate to be present. Even with these limitations, they found:
 Spontaneous mutations were more frequent in patients with autistic spectrum disorder (14/195) than in unaffected individuals (2/196).
 The frequency of spontaneous mutations was higher (12/118) in sporadic cases of autism – children with no affected relatives – than in cases from multiplex families (2/77).
 The frequency of spontaneous mutations in unaffected individuals was 1% (2/196).
 Most of the mutations in autistic individuals were deletions (12/15 – one child had two mutations), while the two mutations in the controls were duplications.
 None of the mutations were seen more than twice and most were seen only once.
 The mutations seen in autistic children were on chromosomes 2, 3, 6, 7, 10, 12, 13, 15, 16, 20 and 22.
If, as they suspect, their technique was only able to pick up 15% of mutations, then the actual mutation rate in autistic children may be much higher.
What it means is that there is a statistically significant (p less than 0.0005) association between spontaneous mutations and autism. Now, I've often argued that association is not causation, and so do the authors of this study.
However, the locations of many of the mutations were highly suggestive of a connection. For instance, one mutation - a 1.1 Mb deletion from chromosome 20 - deleted 27 genes, including the oxytocin gene OXT. This is particularly notable, as oxytocin has been shown to regulate social behavior and awareness.
Five of the mutations involved only a single gene, which indicates that these genes are prime candidates for further study.
Now, what does this mean for the people who claim that autism can’t be genetic, that it’s all the result of exposure to (fill in the blank with environmental toxin de jour)?
Well, it means that they need to start thinking up a way to “spin” these results.
Doubtless, they will find that some of the authors have – at one time in their careers – been supported by the pharmaceutical industry (“Big Pharma”) or “the government” or maybe they’ve ridden in black helicopters.
Or they’ll find some other equally ridiculous claim of bias, corruption or conspiracy.
But they won’t be able to stem the tide.
"What tide?", you ask.
There’s a tidal wave of data bearing down on the “reality deniers” in the autism world, and they’d better start heading for higher ground.
Or learning how to swim.
Note: Prometheus will be attending a conference of minor mythological figures next week and will not be able to moderate comments. Rest assured, when he returns, all pending comments will be dealt with in a firm but fair manner.