CPG Island identification and mapping in the autistic disorder region on chromosome 15q11-q13

Chromosome 15q1l-q13 has been implicated in the genetic etiology of autistic disorder (AutD). To identify candidate AutD genes, a physical map was generated from the GABRB3 receptor to the OCA2 gene. To identify AutD candidate genes within the genomic contig, 28 BAC, PAC and P1 clones containing numerous rare restriction sites were analyzed using Island Rescue PCR (IR-PCR). 150 EagI, BssHII and SacII related CpG island sites were cloned, sequenced and analyzed. BAC/PAC sequence comparison analysis identified 45 unique CpG islands that met full CpG island criteria. 31 CpG island clones were mapped onto the human genomic draft contigs spanning the region from GABRB3 gene to the APBA2 gene. 14 CpG clones including GABRG3 and APBA2 showed expression in human fetal brain tissue. 38 IR-PCR clones did not meet CpG island criteria. 13 clones showed expression in human fetal brain tissue. Five known genes including GABAA receptor subunits, APBA2, and numerous ESTs colocalized with CpG islands in this region and are candidates with AutD gene(s). Currently, we are investigating CpG island SNPs in this region for association with AutD. This island rescue system will allow us to investigate the methylation status and alterations of genes within the AutD region in tissues.