When scientists announced that they had unravelled the map of the human genome in the year 2000 the possibility of answering the question "Is autism genetic?" came one step closer. Somewhere in the region of 25,000 genes have now been isolated, giving researchers the immense task of identifying how each particular gene encodes the development of human growth. Identifying the genetic source of diseases could pave the way for the development of appropriate genetic treatments and the prevention of currently incurable conditions. No definitive gene has been identified as yet, but researchers are slowly closing in on their target.

genetic markersCurrent research in the field of autism has focused on a number of candidate genes and chromosomes. Researchers search for candidate genes by analysing the genetic makeup of people who already have autism and looking for repeated patterns of difference in their genetic code. Positional candidate genes, as they are known, are identified by their occurrence in chromosomes suspected of being closely involved in the development of autism. Functional candidate genes, on the other hand, provide a second source of investigation, and are those genes identified as being responsible for another medical condition that is associated with autism. For instance, the increased levels of serotonin in autistic patients has lead to an interest in genes identified with serotonin production.

Functional candidate genes include the DbH gene (serum dopamine betahydroxylase gene) on chromosome 9 which is associated with neurotransmitter activity, and 5-HTT (serotonin transporter gene) on chromosome 17, as mentioned above.

The chromosomes most associated with genetic research into autism are:

  • Chromosome 2 - at least three different research teams are researching a link between regions of chromosome two and autism, and two of these teams have identified particularly convincing evidence of chromosome 2's involvement in the development of autism with associated language delay.
  • Chromosome 3 - The GAT1 gene and OXTR gene on chromosome 3 are both candidates. GAT1 is associated with the production of a neurotransmitter called GABA which causes overstimulation of the brain. Meanwhile OXTR is thought to be responsible for the production of oxytocin, a chemical found to cause repetitive behaviours in animal studies.
  • Chromosome 7 - FOXP2, WNT2, RELN, HOXA1, HOXB1. These genes are thought to be responsible for the development of language disorders including verbal dyspraxia, the organisation of cellular growth in the foetus and adult nervous system, the foetal development of the brain, and the development of the hindbrain. 
  • Chromosome 15 - GABA, UBE3A, ATP10C.  A region of the chromosome may contain the GABA genes responsible for proteins that carry nerve receptor information. UBE3A is also present on this chromosome and is a candidate due to its association with Angelman Syndrome. ATP10C is thought to help in production of a protein that contributes to the transmission of ions.
  • Chromosome X - MeCPT2, NLGN3/4. MeCPT2 has been identified as being responsible for Rett Syndrome, a condition within the autistic range, and NLGN3/4 have been identified with the production of neuroligin proteins responsible for chemical massaging between neurons. 

genetics and environment Most researchers looking into the question "Is autism genetic?" feel that no one single gene will be identified as the cause of autism, but rather a constellation of genes will be finally given as the cause. Environmental factors will also play a part in activating some genes and therefore it is generally felt that autism is both a genetic and an environmental condition, caused as much by a genetic propensity as by activating environmental conditions. Identical twin studies show that in 10-40% of cases one of the twins will not be diagnosed autistic, suggesting that genes are not the only factor. Environment must play a part.  An example of this may be dietary concerns in pregnancy, and the existence of certain chemicals during foetal development, etc. Current thinking suggests that several hundred genes may contribute to autism and each of these will interact with the environment in different ways. A recent article in the journal Epidemiology, titled "On the complex relationship between genes and the environment in the etiology of autism," examines how the search for genetic answers will always involve some analysis of wider world. 

Recent Research Findings

One piece of interesting recent research may explain why boys are more likely to be diagnosed with autism than girls. Girls, it seems, have a greater number of genetic mutations than boys, suggesting that it may take a largr genetic change for girls to be diagnosed. It is estimated that autism is 90% heritable, but that at least 50% of cases are caused by incidences of spontaneous mutation. Research by a team lead by Michael Wigler examined the DNA of more than 1000 autistic individuals with non autistic parents looking for mutations that delete or duplicate areas of the genetic code. The findings of this research show at least 130 different sites in the genome could contribute to the condition; whilst the team think that the actual number could be in excess of 400. Such a discovery suggests that it is going to be extremely difficult to develop therapies for the whole range of causes. The fact that girls require a greater number of mutations does however give hope that by understanding female resilience to the condition scientists will be able to activate those resistances in boys.

More recent findings from a study of 3000 children with autism suggest that a variation in the gene for transducin beta-like 1X-linked (TBL 1X) may be a significant factor in the development of foetal neurology and the later diagnosis of autism. While another study involving a much smaller cohort of 16 people has linked the condition to the presence of chromatin structures at hundreds of neuronal sites in the prefrontal cortex. Chromatin is the chemical framework of chromosomes. The research team examined genome samples for evidence of histone methylation, a process that indicates epigenetic abnormalities. Histones are tiny particles that attach themselves to DNA strands and effect gene activity. Literally hundreds of loci across the genome were found to be affected. One final study addressing the question "Is autism genetic?" has identified autistic children as having both a larger brain weight and 67% more neurons in the prefrontal cortex, the part of the brain responsible for communication, cognitive development and higher order social development. The significance of this finding rests on the fact that cortical neurons are generated prenatally, indicating a disturbance in molecular and genetic mechanisms during foetal development.