AUTISM- a genetic disorder

Palak Singh1 and Kumar Sourav2 (School of Biotechnology)

Autism is a neural development disorder. It has a strong genetic basis. Autism spectrum is found to occur due to some rare mutations with major effects or by rare multigene interactions of common genetic variants. The complexity increases due to the multigene interactions, the environmental factors or epigenetic factors which donot change DNA but are heritable and influence the gene expression. Environmental factors that have been claimed to contribute to or exacerbate autism, or may be important in future research, include certain foods, infectious disease, heavy metals, solvents, diesel exhaust, PCBs, phthalates and phenols used in plastic products, pesticides, brominated flame retardants, alcohol, smoking, illicit drugs, vaccines, and prenatal stress. Epigenetic mechanism is supported by the discovery of increased MECP2 promoter methylation associated with decreased MeCP2 protein expression in autism male brain. Bisulfite sequencing analyses of a region 0.6 kb upstream of MECP2 in brain DNA samples revealed an abrupt transition from a highly methylated region in both sexes to a region unmethylated in males and subject to XCI in females. Chromatin immunoprecipitation analysis demonstrated that the CCTC-binding factor (CTCF) bound to this transition region in neuronal cells, consistent with a chromatin boundary at the methylation transition. Male autism brain DNA samples displayed a slight increase in methylation in this transition region, suggesting a possible aberrant spreading of methylation into the MECP2 promoter in autism males across this boundary element. In addition, autistic female brain DNA samples showed evidence for aberrant MECP2 promoter methylation as an increase in the number of bisulfite sequenced clones with undefined XCI status for MECP2 but not androgen receptor (AR). Two commonly used diagnostic techniques in autism research are the Autism Diagnostic Interview-Revised (ADI-R) which is a semistructured parent interview, and the Autism Diagnostic Observation Schedule (ADOS) uses observation and interaction with the child. Popular biologically based treatments include supplements, specialised diets, immune therapies, gastrointestinal treatments, chelation, and withholding immunisations. Other non-biological treatments include manipulative and body-based treatments (eg, craniosacral manipulation, and auditory integration), mindbased and body-based therapies (eg, yoga), and energy medicine. Latest treatment technique which is being worked upon involves gene therapy, in which the malfunctioning gene is first identified and then replaced by a healthy sequence. Keywords- Epigenetic, Immunoprecipitation, Craniosacral, Methylation.