Utilization of high density Oligo/SNP array to analyze patients with autism - a step towards high definition GENOMICS

ABSTRACT

Array comparative genome hybridization [aCGH] has been a powerful tool that allows a high resolution whole genome analysis of copy number variations and single nucleotide polymorphisms [SNPs] that can reveal submicroscopic deletions, duplications loss of homo or heterozygosity [LOH] and uniparental disomy. We present aCGH analysis data of 4 patients referred with autism that was analyzed using a high density oligo/SNP array with over 1.9 million markers for copy number variations [CNV's] and about 750,000 SNPs [Affymetrix]. After careful evaluation, we found no genomic CNVs that were previously described but noticed several regions with loss of heterzygosity [LOH] in 2 of the 4 patients analyzed. The regions of LOH range from 7Mb to over 29Mb in patient A2 and from over 3Mb to over 63Mb in patient A3. Some of the LOH noticed in these patients are seen associated with genes responsible for causing Autism. The genes noticed have been fully characterized and classified as Autism genes. Patient A2 has only one gene involved [DPP10 [2q14.1]] and patient A3 has 5 genes [MBD5 [2q23.1], SCN1A, SCN2A [2q24.3], KCTD13 [16p11.2] and PAFAH1B1 [17p13.3]]. Several regions of LOH detected in these two patients encompass -101 Mb and 201 Mb of the total genome respectively. The results suggest that it is not related to a specific disorder but involvement of at least gene in the LOH region can raise the possibility of a recessive condition. The importance of LOH and the details of the genes will be discussed