What is your first thought when you see or hear the word 'mutation'? Does it invoke a positive or negative image? Does it suggest 'difference' or does it suggest 'diversity'?
If I'm honest, the first thing I think about when I see or hear the word 'mutation' is the X-Men. I don't know whether it is because that fabulous Marvel comics franchise has just released another X-Men movie or because it takes me back to my childhood reading comic book days about the exploits of a group of people, who for one reason or another are 'different', championing good over evil (or evil over good if you are that way inclined) with some fantastic super-powers to boot.
Indeed, mutation is one of a number of common threads throughout the Marvel series. Spiderman, the Hulk, the Fantastic Four - all mutated by some force or factor; ordinary people turned into extraordinary heroes. Without trying to philosophise too much, the X-Men brand in particular, brings the issues of difference and diversity to the forefront with its discussions on how mutation leads to difference, and how difference can sometimes bring out both the best and worst of human emotions and behaviour. Comparisons have already been made between the X-Men films and autism.
I digress. The reason for the questions and post is the recent media interest in several studies appearing in the journal Neuron. The studies, whose details can be found here, are all related to our old friends CNVs and in particular how finding lots and lots of CNVs paints a very complex picture of the genetics of autism. To reiterate, CNVs are the losses and gains in genetic material.
I am not going to go through all the studies with my 'questioning answers comb' but will rather reflect on the conclusions cumulatively reached from the papers. The first reflection follows my previous CNVs post in that when looking at the genetics side of things, autism is a complex condition.. nay, a very complex condition. This research kinda confirms what everyone already knows in inferring that there is probably no one set Mendelian pattern of inheritance when it comes to autism - so unlike hair and eye colour, any potential pattern of transmission (either of 'autism' or the various symptoms) is going to be complex. Need some evidence? Have a look at the work being done on the broader autism phenotype.
The second point to make is the fact that where genetic mutations do occur in autism, there is a sizable possibility than some of them are going to be spontaneous in terms of how they come about. I do find some issue with the word 'spontaneous' in that this kinda suggests there is no order or logic behind where or why they occur. My rough-and-ready translation of 'spontaneous' in this context is that the current state of knowledge does not know why something occurs but might do some day. We perhaps had the same issue with PKU before it was known and labelled as PKU as to why some children just 'spontaneously' developed learning disabilities or even worse died. Using the Marvel model, could environment play a role in these spontaneous mutations? Probably, if not why do various animals, including humans, develop drug resistance?
A third point relates to co-morbidity. From what I gather, one or more of the teams looked at children with autism and their unaffected siblings. They then compared and contrasted and found spontaneous CNVs in 8% of the children with autism, compared with 2% of their siblings. OK the differences are not startling but they are there. I have touched upon this point before however in that when we use the word 'autism' all we are really doing is describing a set of diagnostic characteristics derived from behavioural observation and analysis of developmental history. Given that autism does not just 'magically' exist on its own and people with autism as a group carry just about the same likelihood of various co-morbid conditions as anyone else (iron deficiency, diabetes, bowel problems, etc), what's to say that the various CNVs detected were not related to one or more co-morbidites and some perhaps nothing to do with their autistic symptoms? The paper by Gilman and colleagues gives us a clue to this phenomena in action when they say that the identified genes in their study have also been found in intellectual disability phenotypes. Remember also the early test for learning disability.. sorry autism post?
There are other points to make but I will stop there. Don't get me wrong I am certainly not 'geneticist-bashing' when I highlight such issues. Indeed, there are some very interesting questions arising from these collective papers on things like girls and autism genetics. Levy and colleagues ask a very interesting question about the 'fate' of female carriers of the identified CNVs. Could one fate be that of the link between cognitive styles in autism and eating disorders? The points I do however make are that (i) mutation is an important part of human life, and (ii) whilst genetics are no doubt important to autism, these papers reiterate that the role of genes is complex and perhaps not necessarily in isolation from our environment.
I finish with a song about a very different kind of hero.