Autism Spectrum Disorders (ASD) represents a genetically complex developmental disorder. Several approaches have been used to find candidate genes linked to/ or associated with ASD. These include genome wide scans, linkage studies of multiplex families, cytogenetic studies and copy number variation [CNV]. These different approaches have yielded a number of associated and susceptible genes and high risk loci. Single base pair substitutions in NLGN3, NLGN4, SHANK3 and PTEN genes were identified in rare cases of ASD with different degrees of severity. Whole genome screening in multiplex families shows that several genes (2-10 genes) may interact to generate the clinical phenotype.
Utilize whole genome scanning methods in highly inbred families with two or more affected members to map susceptibility loci for Autism Spectrum Disorders.
Methods: This is a report from an ongoing approved research project of studying multiplex ASD families in Saudi Arabia using Affymetrix GeneChip® Human Mapping Arrays. We have so far recruited 13 families with 2-4 affected individuals per family. The diagnosis of ASD was established by two independent evaluations by experienced clinicians utilizing DSM-IV criteria. In addition, many individuals underwent evaluations using Autism Diagnostic Observational Schedule (ADOS ) module I and / or Autism Diagnostic Interview – Revised ( ADI-R). Children were also evaluated by a multidisciplinary team specialized in evaluating children with ASD.
Analysis of 250K microarray data on both affected and unaffected individuals from each family independently revealed a number of loci in these families in which some may represent novel loci. Our data confirms the genetic heterogeneity and complexity of the disorder.
The large number of loci and chromosomes associated with ASD fit the model for a complex genetic syndrome, in which more than one locus may contribute to high risk and increased susceptibility to a broad spectrum phenotype. The current and recent reported studies suggest that whole genome scanning methods in highly inbred families are of high yield and might lead to the discovery of new susceptibility genes for ASD which will help in clarifying the biological basis for ASD.