Genetic Studies of Autism Spectrum Disorders

This study utilized genetics, bioinformatics, and neuroscience programs at Children’s Hospital Boston to address the genetic basis of autism spectrum disorders (ASD). One hypothesis of this study was that there are genetic variants that may predispose an individual to develop ASD, and that these genes can be identified by transmission disequilibrium testing (TDT) of candidate genes in pathways logically indicated based on gene expression and neuronal activity studies. Using TDT and trios (child with autism and their parents), and affected sib pairs (ASP) analysis, studies were performed to look for association of ASD with candidate genes and for linkage peaks associated with ASD. Another hypothesis of this study was that there would be differences in gene expression in the white blood cells of children with autism in comparison with normal children. Microarray analysis was performed to study differences in gene expression in white blood cells of children with autism compared with that of normal children. Sparked by evidence that autism may be caused by defective synaptic maturation and the finding that activity-dependent gene transcription plays a role in synapse maturation, a third hypothesis of this study was that mutations of transcriptional regulators and their target genes may underlie some forms of autism.