INSIGHTS FROM GENETICS
There was a time when autism was believed to be entirely psychological, the result of rejecting, cold parenting. This was completely untrue, as scientists, researchers, and clinicians came to realize. (See Refrigerator Mothers – A Discredited Theory.) It is now widely accepted that a complex combination of genetic factors plays some role in the Autism Spectrum Disorders (ASDs). 1
Twin Studies, Family Studies, and the "Broad Autism Phenotype"
One way we know there is a substantial genetic influence in autism is through twin studies. Researchers compare twin pairs –both identical and fraternal (that is, non-identical) pairs—to see if the pattern of a disease or trait’s inheritance differs between them. This is useful because identical twins share 100% of their genetic material, while fraternal twins share only about half. If you find much higher rates of a disease or shared trait between identical twins as compared to fraternal twins, you’ve got evidence that genetic factors are key. Various twin studies focused on autism have shown a degree of similarity, as far as autistic traits are concerned, for the identical twins of 60% to 90%, but only 0% to 10% for the fraternal twins. 2 A recent study based on 277 twin pairs participating in the IAN project resulted in similar findings: in 88% of identical twin pairs, both twins had some form of autism spectrum disorder, but this was the case in only 31% of non-identical twin pairs.3
Additional evidence is provided by family studies. In these investigations, researchers take a look at the siblings of individuals known to have autism. If the rate of autism among these siblings is much higher than the rate found in siblings of non-autistic individuals, we have more evidence that ASD has a genetic basis. This has been found to be the case: “Various family studies have demonstrated a sibling recurrence risk of 2% to 6%. This risk is significantly higher than that in the general population, which even at its highest estimate is still less than .5%.” 4
As they began to look at the families of individuals with an ASD, investigators discovered another crucial fact: various autistic traits, including social deficits, anxious-rigid behaviors, and obsessive-compulsive tendencies, were frequently observed among non-autistic family members. It is now widely accepted that there is a broad autism phenotype, that is, a collection of specific autistic-like traits that run through families. 5 Unfortunately, we still don’t know exactly how this all works. Writes one notable researcher:
Questions arise as to whether the broader phenotype represents a lesser “dose” of genetic liability, a different pattern of susceptibility genes, or some kind of “two-hit” mechanism, in which some additional risk factor is required in order to take individuals over the threshold from the broader phenotype to a more seriously handicapping disorder. 6
Hopefully, realizing that milder versions of autistic-like traits run in families will help those of us in an ASD family better understand our own relatives (or ourselves) with regard to anything from negative aspects, like obsessive interests or social anxiety, to positive assets, like talent in mathematics or the ability to pay great attention to detail. One study actually found that children with autism, who presumably have a detail-oriented, parts-focused cognitive style, are more than twice as likely to have fathers and grandfathers who are engineers as compared to non-autistic children. 7
To summarize the above: twin studies, family studies, and the existence of the broad autism phenotype all demonstrate that Autism Spectrum Disorder is “among the most heritable of all neuropsychiatric disorders.” 8 There is no question that genetics are a factor in ASDs.
Finding the Genes
There are believed to be anywhere from 2 to 20 interacting genes that contribute to autism susceptibility, 9 and scientists have begun to search for the genes that, in combination, result in ASD. The process of identifying these would be complicated even if ASD were not so variable. The fact that there are a whole cluster of traits and a “spectrum” of disability makes the entire undertaking even more difficult.
Clues are being followed down several avenues. For one thing, there are some conditions with a known genetic basis that resemble or overlap with autism, including Rett Syndrome, Fragile X Syndrome, and Tuberous Sclerosis Complex. Investigating whether the genetic factors known to be involved with these are linked to autism as well may yield some answers. In addition, families with more than one member with an ASD are being studied in an attempt to find candidate genes for autism. Another approach is to focus in on specific autistic traits –called endophenotypes-- such as social deficits or repetitive behaviors, rather than autism as a unitary concept. If different genes are responsible for different aspects of ASDs, untangling which genes are associated with which deficits is a crucial step, and one that will help simplify investigation. 10
A New Genetics Theory for Autism: Sporadic and Inherited Mutations
The first ever peer-reviewed paper to be published using IAN data described a revolutionary new genetic theory for how autism is acquired. In contrast to the notion that we must find an autism susceptibility gene that might be present across the world and the genome (that is, the genetic material of all the people in the world), this theory hypothesized that spontaneous mutations of genes are causing autism. 11
For the majority, such a mutation would have happened within a parent's sperm or egg cell. The child resulting from this sperm or egg would have autism. Because this occurred in a single sperm or egg, however, the family would be unlikely to have a second child with an ASD.
There would be a minority of families, however, in which such a mutation was now passing down through the generations. In such families, autism would be something you could inherit from a parent carrying the mutated gene. The risk of having a second child with autism for such a family would be much higher.
For a detailed explanation of this new theory, see "A Unified Genetic Theory for Sporadic and Inherited Autism."
Copy-Number Variations: Deletions and Duplications
There has been yet another new type of finding regarding genetics and autism.12 Researchers have found that copy-number variations (or CNVs) may play a very major role. These are not mutations of genes -- that is, single genes that have been altered -- but genetic material that a person has too little or too much of. Theoretically, we should each have two copies of each gene in our genetic code -- one that we received from our father, and one that we received from our mother. When a person has a copy-number variation, then he or she has zero, one, or three copies of entire strands of DNA. These strands of DNA may include less than one gene, a single gene, or whole sets of genes, depending on how long the strand of DNA is. Copy-number variations on a certain region of Chromosome 16 have been associated with a high risk of autism spectrum disorder.
For a detailed explanation of this new theory, see "Microduplications and Microdeletions on Chromosome 16."
Many Mutations - Similar Effects
A study published in Science in July 2008 announced the discovery of six new genes associated with autism.13 Whether deleted or mutated, each genetic problem led to similar effects: disruption of the brain's ability to form connections based on learning.
The genes were discovered by studying families from the Middle East, Turkey, and Pakistan. In such families, first cousins often marry, and families are large, so that rare genetic defects are concentrated and more easily identified. An intriguing finding was that many of the genes involved are switched "off," providing hope that treatments can be found that would switch them back "on." The findings also provided some support for current intensive behavioral treatments, as these might be imagined to help build connections in the brain that did not form naturally as a result of the genetic defect.
Read the in-depth Children's Hospital of Boston press release, complete with diagrams.
We still do not know exactly how many genes, in what combinations, result in what type of Autism Spectrum Disorder, or if it is only spontaneous genetic mutations or copy number variations that cause autism. (Any one of all of these may be at work in certain cases.) Neither do we know if there are specific environmental triggers that can “activate” or "turn off" certain genes, making a child “get” an ASD when they wouldn’t have otherwise, or that cause certain genes in a sperm or egg to mutate, causing autism. There is a great deal of work to be done before the genetic picture comes into complete focus.
Genes alone do not explain autism, however. What we also need to understand is how a specific gene ultimately affects the structure and chemistry of the brain and, therefore, cognition and behavior. How are the brains of individuals with an ASD different from those of “typical” people? To truly understand what is going on with autism, we will have to understand how the functioning (or malfunctioning) of a certain gene leads to abnormal brain structure, circuitry, and chemistry. (See Insights from Neuroscience.)
- Rutter, M. (2005). Genetic influences and autism. In F. Volkmar et al. (Eds.), Handbook of Autism and Pervasive Developmental Disorders (pp.425-452). Hoboken, NJ: John Wiley & Sons.
- Rosenberg, R.E., Law, J.K., Yenokyan, G., McGready, J., Kaufmann, W., & Law, P.A. (2009). Characteristics and concordance of autism spectrum disorders among 277 twin pairs. Archives of Pediatrics & Adolescent Medicine, 163(10), 907-914. View Abstract
- Spence, S.J. (2004). The genetics of autism. Seminars in Pediatric Neurology, 11, 196-204. View Abstract
- Spence, S.J. (2004). The genetics of autism. Seminars in Pediatric Neurology, 11, 196-204. (pg 196). View Abstract
- Piven, J. (2001). The broad autism phenotype: A complementary strategy for molecular genetics studies of autism. American Journal of Medical Genetics (Neuropsychiatric Genetics), 105, 34-35. View Abstract
- Rutter, M. (2000). Genetic studies of autism: From the 1970s into the millennium. Journal of Abnormal Child Psychology, 28(1), 3-14. (pg 7). View Abstract
- Baron-Cohen, S., Wheelwright, S., Bolton, P., & Goodyer, I. (1997). Is there a link between engineering and autism? Autism 1(1), 101-109. View Abstract
- Spence, S.J. (2004). The genetics of autism. Seminars in Pediatric Neurology, 11, 196-204. (Pg. 196). View Abstract
- Spence, S.J. (2004). The genetics of autism. Seminars in Pediatric Neurology, 11, 196-204. (pg 198). View Abstract
- Geschwind, D.H., & Alarcon, M. (2006). Finding genes in spite of heterogeneity: Endophenotypes, QTL mapping, and expression profiling in autism. In S. Moldin & J.L.R. Rubenstein (Eds.), Understanding Autism: From Basic Neuroscience to Treatment (pp.75-93). Boca Raton, London, & New York: Taylor & Francis.
- Zhao, X., Leotta, A., Kustanovich, V., Lajonchere, C., Geschwind, D.H., Law, K., Law, P., Shanping, Q., Lord, C., Sebat, J., Ye, K., & Wigler, M. (2007). A unified genetic theory for sporadic and inherited autism. Proceedings of the National Academy of Science, 104(31), 12831-12836. View Abstract
- Weiss, L. A., Shen, Y., Korn, J. M., Arking, D. E., Miller, D. T., Fossdal, R., et al. (2008). Association between microdeletion and microduplication at 16p11.2 and autism. The New England journal of medicine, 358(7), 667-75. View Abstract
- Morrow, E.M., Yoo, S.Y., Flavell, S.W., Kim, T.K., Lin, Y., Hill, R.S., et al. (2008). Identifying autism loci and genes by tracing recent shared ancestry. Science, 321, 218-223. View Article