Session 3: Molecular Genetics of Autism
Moyra Smith , M.A. Spence
University of California, Irvine
There is evidence from linkage studies (Bass et al., 1998) and from cytogenetic studies (Steffenburg et al., 1996, Cook et al. 1997, Schroer et al. 1998) that a locus on chromosome 15q11-q13 plays a role in the development of autism. We have identified a deletion in the chromosome 15q22-q23 region in a patient with autism, developmental delay and mild dysmorphism (Smith et al 2000). We determined that the deletion in our patient is approximately 2.5 megabases in length and that she is hemizygous for at least 13 genes. The deletion in this patient occurred in close proximity to a chromosome 15 specific duplicon that contains coding sequence for a golgin like gene. In searching DNA sequence in Genbank we determined that golgin related duplicons occur in four segments of chromosome 15. The golgin repeat containing duplicon that we identified on chromosome 15 is likely identical to that reported by Pujana et al. 2001. They noted that 13-22 kb duplicons containing sequences highly homologous to a golgin like protein and a SH3 domain protein, occur in three regions on chromosome 15, 15q11-q13, 15q23-q24 and 15q26.
Duplicons are known to predispose to chromosome rearrangements. It has been proposed that the presence of expressed sequences within duplicons may further stimulate recombination (Chen et al 1997). It is likely that the duplicons on chromosome 15 that contain sequences homologous to golgin and SH3 domain protein predispose to chromosomal rearrangements. Ji et al (1999) reported that duplicons containing HERC2 gene sequences are located in the 15q11-q13 region and predispose to rearrangements in that region.
It is therefore likely that intra-chromosomal deletions and duplications of chromosome 15 are not uncommon. Such rearrangements may be missed in routine cytogenetic studies. The question then arises, which chromosome 15 rearrangements lead to autism and by what mechanism? Are genes of similar or related function deleted or duplicated in the different cases of chromosomal 15 rearrangement that manifest autistic disorder? Do different deletions or duplications lead to autism because they result in altered development of specific regions of the brain, albeit through different mechanisms? Are there genes on chromosome 15 that have similar or related functions to genes in other regions of the genome that are associated with autism.
Back to Agenda