Chromosome 9: The DbH gene (serum dopamine ß-hydroxylase gene)
Serum dopamine ß-hydroxylase (DßH) is thought to play a role in the way that the neurotransmitters dopamine and norepinephrine work. Because previous studies have shown that children with autism in certain families have low levels of DßH in their blood, a group of researchers (Robinson et al, 2001) looked at the gene that produces DßH as a potential candidate gene. These researchers studied versions of the DßH gene in families with two or more siblings with autism. Although they did not find that siblings with autism shared a specific version more often than would be expected by chance, they did find that mothers of children with autism had a specific type of the DßH gene (called the "DßH-" variation) more often than mothers of children without autism. The "DbH-" variation was associated with lower than average blood level of DbH enzyme activity. These researchers theorized that this lower enzyme level might create differences in the uterus during pregnancy, perhaps resulting in autism in some families when combined with other unknown genetic factors. The DbH gene is also an interesting candidate gene because it lies close to the gene that causes tuberous sclerosis on chromosome 9. Tuberous sclerosis has been reported to sometimes be associated with autism.

Chromosome 17: The serotonin transporter gene (the 5-HTT gene)
As mentioned above, the serotonin transporter gene has been considered to be a good candidate gene for autism, and has been studied extensively. Unfortunately, research so far has not revealed any consistent associations between different versions of the serotonin transporter gene and autism. For example, several researchers have studied variations in an area near the serotonin transporter gene called an "upstream regulatory region." Regulatory regions influence the activity of genes, and therefore can be involved in causing genetic disorders if they don't function properly. Some researchers (Cook et al., 1997) have found an association between one type of variation in this region and autism. Other researchers (Klauck et al., 1997; Yirmiya et al., 2001) have reported an association between a different variation in this region and autism. Still other researchers (Maestrini et al., 1999; Zhong et al., 1999; Persico et al., 2000) have found no association between variations in this region and autism. Scientists working to study other types of variations in different parts of the serotonin transporter gene have not reported any significant associations between the gene variations and autism (Cook et al., 1997; Klauck et al., 1997; Maestrini et al., 1999). While these different results are confusing, they reflect the complexity of studying the genetics of autism. Further research is necessary to better understand what role, if any, the serotonin transporter gene may play in the development of autism.

1. Cook et al. (1997): Authors used TDT (Transmission Disequilibrium Test) with 86 singleton families (both parents and one affected child) to investigate possible association of two polymorphisms of the 5-HTT gene: a common polymorphism in the upstream regulatory region, called 5-HTTLPR, and a VNTR in intron 2. They found evidence of association with the short allele of 5-HTTLPR. In contrast, no preferential transmission was observed for any of the alleles of the VNTR polymorphism.



2. Klauck et al. (1997): Association study using TDT was performed for the 5-HTTLPR promoter polymorphism, the VNTR in intron 2 of the 5-HTT gene, and haplotypes of both loci in 65 autism trios. Higher frequency and preferential transmission of long allele of 5-HTTLPR was observed. No evidence for linkage disequilibrium was observed between autism and the VNTR in intron 2.



3. Zhong et al. (1999): Authors analyzed 5-HTTLPR genotypes of 72 autistic subjects, 11 patients with fragile X and autistic behavior, 43 normal subjects, and 49 patients with fragile X and no autistic behavior. Distribution frequencies of long and short alleles showed no differences between subjects.



4. Maestrini et al. (1999): Association study using 90 mostly multiplex families from IMGSAC (International Molecular Genetic Study of Autism Consortium), looking at 2 polymorphisms in the 5-HTT gene:a functional insertion-deletion polymorphism in the promoter (5-HTTLPR) and a VNTR in intron 2. No evidence of linkage or association was found with either marker.



5. Persico et al. (2000): The 5-HTT promoter repeat (5-HTTLPR) was genotyped in 54 singleton families from Italy, 32 singleton families from US, 5 multiplex families from US, for a total of 98 trios. The data were analyzed with the TDT. No evidence of linkage/association was found between 5-HTT promoter alleles and autistic disorder.



6. Tordjman et al. (2001): Transmission of the long and short alleles of the 5-HTT promoter polymorphism (5-HTTLPR) was examined in families of 71 children with autism using TDT. Transmission of alleles did not differ between probands and their unaffected siblings, but allelic transmission in probands was dependent upon severity of impairment in social and communication domains, with greater short allele transmission in severely impaired individuals and greater long allele transmission in mild/moderately impaired individuals.



7. Yirmiya et al. (2001): Excess of long/long 5-HTTLPR genotype observed as well as preferential transmission of long allele in 35 autism families.

X chromosome: MAO A promoter, MECP2

HOW GENES ARE NAMED
You may wonder how genes are named. As you may have guessed, some names are abbreviations for the full gene names. Other genes are named after similar genes in other organisms. More ...

WHAT IS A CHROMOSOME?
Chromosomes are structures that contain genes. Chromosomes are visible with a microscope and are located in the nucleus of a cell. Almost every human chromosome contains thousands of individuals genes. More ...

HOW CHROMOSOME ABNORMALITIES HELP US FIND GENES
Genetic researchers use many different tools and strategies to look at the genetic material (DNA) inside our cells to find the exact gene(s) that cause a genetic disorder such as autism. More ...

HOW GENOME SCREENS HELP US FIND GENES
In order to determine the genes that may be involved, scientists also perform what are referred to as "genome screens." To do this they use maps of the chromosomes in order to look for genes. More ...