Replication of the Association between Copy Number Variation on 8p23.1 and Autism by Using ASD-specific BAC Array

To discover genetic markers for autism spectrum dis-order (ASD), we previously applied genome-wide BAC array comparative genomic hybridization (array-CGH) to 28 autistic patients and 62 normal controls in Korean population, and identified that chromosomal losses on 8p23.1 and on 17p11.2 are significantly associated with autism. In this study, we developed an 8.5K ASD-specif-ic BAC array covering 27 previously reported ASD-asso-ciated CNV loci including ours and examined whether the associations would be replicated in 8 ASD patient cell lines of four different ethnic groups and 10 Korean normal controls. As a result, a CNV-loss on 8p23.1 was found to be significantly more frequent in patients re-gardless of ethnicity (p＜0.0001). This CNV region con-tains two coding genes, DEFA1 and DEFA3, which are members of DEFENSIN gene family. Two other CNVs on 17p11.2 and Xp22.31 were also distributed differently between ASDs and controls, but not significant (p=0.069 and 0.092, respectively). All the other loci did not show significant association. When these evidences are con-sidered, the association between ASD and CNV of DEFENSIN gene seems worthy of further exploration to elucidate the pathogenesis of ASD. Validation studies with a larger sample size will be required to verify its bi-ological implication.Keywords: 8p23.1, array-CGH, autism, copy number variation, defensin