While scientists anticipate that genetics is involved in autism, no specific genes or gene interactions have been identified. In contrast, the field of "epigenetics," has provided important information about Rett syndrome, which has strong components of autism. Epigenetic alterations do not involve mutations in the sequences of DNA in genes. Rather, epigenetics concerns modifications that occur during cell division in "cytosine," one of the four "base pairs" of chemicals in DNA. The collaborating researchers, one of whom is expert in epigenetics, and the other in neurocognitive functioning in families, hypothesize that specific epigenetic alterations occur in autism. These alterations, they suspect, may affect disease incidence, and probably affect disease severity. The researchers will undertake epigenetic studies of DNA in blood samples from 30 pairs of monozygotic twins, who share the same DNA but have different levels of disease severity. They will look for epigenetic (chemical) changes in DNA that differ in the more severely affected, compared to less severely affected, twin in each pair. They then will confirm these chemical changes using a quantitative method for measuring them at the level of an individual gene. If they are able to identify specific epigenetic alterations that occur in autism, the research will open new avenues for diagnosis and treatment, such as identifying carriers of the epigenetic trait, prenatal testing, and devising new types of treatment for this inherently reversible chemical alteration. Additionally, since specific chemical alterations provide targets for environmental agents, the findings could lead to new ways to prevent or treat these interactions. Significance: If specific chemical alterations in DNA that occur during cell division are found to be associated with autism severity, and possible incidence of the disease as well, it could provide major new understanding of the basis for inheritance, and usher in new approaches to diagnosis and treatment and ultimately prevention of autism.