- To determine if the prevalence of UPD and mosaicism in children with ASDs born to mothers 35 and older is higher than control, typically developing children born to mothers in the same age range.
- To study the epigenetic differences in CG methylation in children with ASDs born to older mothers versus control, typically developing children born to mothers 35 and older.
Methods: For this study, we have assembled a unique, culturally diverse patient cohort of typically developing children and children with ASDs born to mothers 35 and older. We collected DNA from the subjects’ buccal epithelium, a tissue of the same embryonic ectodermal lineage as neurons; a recent study of mosaic trisomy proved buccal epithelium to be a better predictor of brain chromosomal status than blood. To detect mosaic trisomy and UPD we are employing SNP arrays, and have optimized a computational approach to accurately discover these events. We are concurrently analyzing the same buccal epithelial samples using methylation arrays to study potential DNA methylation differences in these populations, as buccal cells may serve as better indicators of brain tissue methylation status.
Results: We are currently completing the molecular assays on our entire patient cohort and are expecting completed results in the next 2-3 months.
Conclusions: The discovery of higher rates of mosaicism, UPD, or epigenetic dysregulation in our ASD cohort will significantly enhance our understanding of the etiology of ASDs, especially in the population of older mothers. The results may also help better direct therapeutic interventions in affected children with an ASD attributed to one of these genetic or epigenetic events.