Researchers in the CPEA Network and their colleagues around the world have learned a lot about autism through genetic studies, but they still have a great deal to learn. To date, some of their findings include the following.

Chromosomes where important genes are likely to be found

Using genome-wide screens, scientists have identified a number of genes that might be involved in autism. Although some analyses suggest that as many as 12 genes might be involved in ASDs, the strongest evidence, points to areas on:

Chromosome 2—Scientists know that areas of chromosome 2 are the neighborhoods for ?omeobox?or HOX genes, the group of genes that control growth and development very early in life. You have 38 different HOX genes in your chromosomal neighborhoods, and each one directs the action of other genes in building your body and body systems. Expression of these HOX genes is critical to building the brain stem and the cerebellum, two areas of the brain where functions are disrupted in ASDs.

Chromosome 7—Researchers have found a very strong link between this chromosome and autism. Their investigations now focus on a region called AUTS1, which is very likely associated with autism. Most of the genome studies completed to date have found that AUTS1 plays some role in autism. There is evidence that a region of chromosome 7 is also related to speech and language disorders. Because ASDs affect these functions, autism may involve this chromosome.

Chromosome 13—In one study, 35 percent of families tested showed linkage for chromosome 13. Researchers are now trying to replicate these findings with other populations of families affected by autism.

Chromosome 15—Genome-wide screens and cytogenetic studies show that a part of this chromosome may play a role in autism. Genetic errors on this chromosome cause Angelman syndrome and Prader-Willi syndrome, both of which share behavioral symptoms with autism. Cytogenetic errors on chromosome 15 occur in up to 4 percent of patients with autism.

Chromosome 16—Genes found on this chromosome control a wide variety of functions that, if disrupted, cause problems that are similar or related to symptoms of autism. For example, a genetic error on this chromosome causes tuberous sclerosis, a disorder that shares many symptoms with autism, including seizures. So, regions on this chromosome may be responsible for certain similar behavioral aspects of the two disorders.

Chromosome 17—A recent study found the strongest evidence of linkage on this chromosome among a set of more than 500 families whose male members were diagnosed with autism. Missing or disrupted genes on this chromosome can cause problems, such as galactosemia, a metabolic disorder that, if left untreated, can result in mental retardation. Chromosome 17 also contains the gene for the serotonin transporter, which allows nerve cells to collect serotonin. Serotonin is involved in emotions and helps nerve cells communicate. Problems with the serotonin transporter can cause obsessive-compulsive disorder (OCD), which is marked by recurrent, unwanted thoughts (obsessions) and/or repetitive behaviors (compulsions).

The X chromosome—Two disorders that share symptoms with autism—Fragile X syndrome and Rett syndrome—are typically caused by genes on the X chromosome, which suggests that genes on the X chromosome may also play a role in ASDs. People generally have 46 chromosomes in most of their cells— 23 from their mother and 23 from their father. After fertilization, the two sets match up to form 23 pairs of chromosomes. The chromosomes in the 23rd pair are called the 'sex chromosomes',X and Y. Their combination determines a person's sex—males usually have one X and one Y chromosome, and females usually have two X chromosomes. The fact that more males than females have autism supports the idea that the disorder involves genes on the X chromosome. Females may be able to use their other X chromosome to function normally, while males, without such a back up, show symptoms of the condition.

Potential candidate genes

By focusing their studies on hot spots, researchers have narrowed their search for candidate genes. They need to do more work to understand how many genes are involved, and how these genes interact with each other and with the environment to cause autism. Researchers do have some promising leads— more leads than can be mentioned in this fact sheet, but these are a few.

Researchers have found evidence that autism may involve the HOXA1 gene. HOXA1, a homeobox gene, plays a critical role in the development of important brain structures, cranial nerves, the ear, and the skeleton of the head and neck. Researchers know that the HOXA1 gene is active very early in life— between the 20th and 24th days after conception—and that any problem with the gene's function causes problems with the development of these structures. Such problems may contribute to the features of autism.

In one study, nearly 40% of the persons with autism carried a specific mutation in the HOXA1 gene sequence—nearly twice as many as those who had the same change, but who did not have autism and were not related to anyone with autism. In addition, 33 percent of those who did not have autism but were related to someone with autism also had the mutation in their HOXA1 gene. These findings mean that autism does not result from genetics alone, but that some other factors are also involved in causing the condition. If researchers can confirm an association between this mutation and ASDs, they may be able to detect the mutation as an early test for autism, allowing important interventions to start as early in life as possible.

Another study found that increased head size in ASD patients was associated with a different mutation in the HOXA1 gene. About 20% of persons with autism have large head size. It is one of the most consistently reported physical features of persons with autism. Now researchers want to know whether the mutation affects head size in persons with autism only, or if it affects head size in general, regardless of ASD status. Several other genes have come forward as potential candidates, including:

The Reelin (RELN) gene on chromosome 7—This gene plays a crucial role in the development of connections between cells of the nervous system. Researchers think that abnormal brain connectivity plays a role in autism, which makes Reelin a good candidate. In addition, persons with autism and their parents and siblings have lower levels of certain types of the Reelin protein, which may mean that gene is not functioning normally.

The HOXD1 gene—This homeobox gene is critical to the formation of certain brain structures. This gene is involved in Duane syndrome, a disorder that causes eye- movement problems and sometimes occurs with autism. In one study of persons with autism, nearly 94 percent of participants had mutations in the same regions of HOXD1, which could mean that the region contributes to ASDs.

Gamma-amino-butyric acid (GABA) pathway genes—GABA compounds are neurotransmitters, which means they help parts of the nervous system communicate with each other. GABA receptor genes are involved in early development of parts of the nervous system and help with communication between these parts throughout life. A problem in the GABA pathway can cause some of the symptoms of ASDs. For instance, epilepsy may result, in part, from low levels of GABA compounds. Many persons with autism also have epilepsy and also show low levels of GABA. Current research focuses on genes that, when their structure or function is incorrect, cause autism-like problems in mice.

Serotonin transporter gene on chromosome 17— The serotonin transporter allows nerve cells to collect serotonin so that they can communicate. Serotonin is a neurotransmitter involved in depression, alcoholism/problem drinking, OCD, and other disorders. Research shows that persons with autism have higher- than-normal levels of serotonin—ranging between 25 percent and 50 percent higher than persons without autism. This higher serotonin level may result from problems with the serotonin transporter that arise from errors in the gene.