If there are cases where a rare mutation in a gene occurs along with a phenotype of autism (or schizophrenia, or ADHD) multiple times, then it doesn’t seem that far off to conjecture that this mutation was necessary for the phenotype, in those individuals. Whether it’s sufficient is up for debate–that may be where environmental effects come in.

This is all a very phenomenological type of “why”–when piece X breaks, phenotype Y can result. This single-gene causality sheds little light, however, on why it makes sense that the system breaks in certain characteristic ways rather than others. This is even more true when it is seen that the same mutations can show up in multiple different disorders. While it may be a small step to suggest that had gene X not mutated, uncommon phenotype Y would probably be absent, a model that can robustly predict whether phenotype Y or Z occurs based solely on knowledge of a few mutations X1, X2, etc. is much more difficult. Even more so, if you try to predict the manifestation of a spectrum disorder, i.e. whether the autism will involve speech difficulty or hyperlexia, for instance–and these are the things that really have meaning for what special accommodations or interventions are necessary.

Things like growth patterns and resource trade-offs are much more likely to capture the failure modes as a whole. Biological systems clearly seem to malfunction in a very different way from human machines. If a brake fluid line is ruptured in a car, it will not cause the steering to become more accurate. The most adaptive we can get with designs is to incorporate redundancy, which delays the consequences of progressive malfunction. Probably the most fascinating characteristic of biological systems, in my opinion, is their ability to “get by with what they have”. Yes, there are things like congenital blindness and deafness where there is simple absence of a trait, but more often there are both extreme losses of function and gains of function in the same disorder.

It is probably more apt to think of an organism like an ecosystem where loss of one species causes die-offs of some species and overgrowths of others. True understanding of biological phenotypes will only come about by understanding the interconnectedness of this “ecosystem”, which is much farther off than “lacking X correlates with end result Y”.

Maybe that didn’t come out quite right. I didn’t mean that you were overselling a particular finding. I mean that EVERYONE oversells these findings. If tomorrow scientists discover that a gene raises the risk of Disease X by 10% the headline the next day will be “Scientists Find Gene That Causes Disease X”. It’s easy to become cynical.

In contrast, previous associations with common SNPs, which supposedly contribute only a tiny increase in risk alone but a large effect in aggregate, have not held up over time. In my opinion, that is because that model of the genetic architecture of illness is not correct – that does not imply (at all) that the illness is not primarily genetic.

“We identified POTENTIALLY causative de novo events in 4 out of 20 probands, particularly among more severely affected individuals, in FOXP1, GRIN2B, SCN1A and LAMC3.”

You wrote that these 4 mutations cause Autism and yet the study abstract says that they are “potentially causitive”.

Over the last 20 years the only common denominator I’ve seen in the field of genetics is oversold findings.

While it’s certainly possible that these 4 genes trigger Autism I wouldn’t bet on it. If history is any guide future research will suggest that they are merely associated with an increased risk of disease or the original discovery was a false positive.

I’m sure if you asked the studies authors they would tell you that the connection between obesity and Autism is in some way related to harmful inflammation or a secondary consequence of harmful inflammation.

The next time you read that a disease is associated with obesity think associated with inflammation. The two are connected like pepperoni and cheese.

http://www.sciencedaily.com/releases/2012/04/120409103942.htm
Maternal Obesity, Diabetes Associated With Autism, Other Developmental Disorders

“…mothers who were obese were 67 percent more likely to have a child with ASD than normal-weight mothers without diabetes or hypertension, and were more than twice as likely to have a child with another developmental disorder.”

“The authors note that obesity is a significant risk factor for diabetes and hypertension, and is characterized by increased insulin resistance and CHRONIC INFLAMMATION, as are diabetes and hypertension. In diabetic, and possibility pre-diabetic pregnancies, poorly regulated maternal glucose can result in prolonged fetal exposure to elevated maternal glucose levels, which raises fetal insulin production, resulting in chronic fetal exposure to high levels of insulin.”

Dr.J.A;E; Gilles

So, could increased body size, of modern neonates, and the accelerated growth seen in a high majority of today’s children, be a result of similar adventures by the human genome, trying top capitalise on novel scaling rules which dictate that it may be possible to reallocate resources through the growth and development phase of human development, because of the reduced perception of danger, regarding the threat of infectious disease, which no longer exists (at least, at a genetic level).

However the recent discovery that hypoxia might underlie congenital birth defects is earth shaking.

http://www.sciencedaily.com/releases/2012/04/120405131220.htm
Nature and Nurture: World‐first Discovery Sheds New Light On Congenital Birth Defects

–excerpt
Dunwoodie’s group then went on to test the genetic risk factor in a mouse model combined with an environmental insult in the form of hypoxia. Surprisingly, they found a marked increase in spinal abnormalities in the offspring, when the mothers were exposed to only 8 hours of low oxygen during an entire 21‐day pregnancy.

“We found that the combination of the genetic risk as well as exposure to low oxygen, resulted in our subjects being up to 10 times more likely to develop congenital scoliosis, than those that only had the genetic risk factor,” says Dunwoodie.

“What this brief period of low oxygen essentially did was disrupt the pathway responsible for development of the spine, and we know that the same pathway is used in the development of limbs and many organs, including the heart, kidneys, brain and cranio‐facial region,” adds Dunwoodie.

Bob Graham, a professor and executive director of the cardiac research institute, says around 25 percent of patients with congenital scoliosis also have some form of congenital heart defect, indicating that a single environmental ‘insult’ such as hypoxia, can potentially affect the development of more than one organ in the body.