ASD is a heterogeneous condition with various contributing factors both genetic and environmental. An apparently Mendelian recessive model of inheritance has been observed in some multiplex families particularly from the Middle East.
Molecular studies of ASD in different populations have provided strong evidence for genetic variability, where different genes and/or loci have been associated or linked to this disorder; therefore, characterizing ASD as one of the complex genetic disorders in which more than one gene may contribute to a broad-spectrum phenotype. Genome wide scans, linkage studies of multiplex families, cytogenetic studies and copy number variation [CNV] have yielded a number of associated and susceptible genes and high risk loci on several chromosomes these include; 1p, 2q32, 5q, 6q21, 7q22,11p12-p13,13q, 16p13, 17q,19p and Xq13-q21. The increased incidence of ASD in Saudi Arabia and the presence of multiplex families with a consanguineous background highlights the importance of and opportunity to determine the genetic basis of this disorder in these families.
Utilize whole genome scanning methods in highly inbred families with two or more affected members to search for shared Loss of Heterozygosity (LOH) regions.
This is a report from an ongoing approved research project of studying multiplex ASD families in Saudi Arabia using 250K Affymetrix GeneChip® Human Mapping Arrays. We have so far recruited 12 families with at least 2 affect individuals. 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 Interview – Revised (ADIR-R).
Affected Sib-pair analysis from each family independently and combined analysis of affected individuals from multiple families revealed a number of shared LOH regions in these families. These regions may harbor candidate genes.
The large number of homozygous regions in affected individuals identified fit the model for a complex genetic syndrome. LOH analysis revealed a number of shared candidate loci between at least 3 families on different chromosomes.