Detecting Genomic Copy Number Variation in Autism Using cDNA Micro-Array Technology
University of Iowa
While the likelihood of an individual developing autism is largely determined by genetic factors, the specificity of these variants has remained elusive due to the fact that most autism genetic studies have tried to find disease-related genetic variants that are either very small, ranging from 1–100 nucleotides in length, or very large, such as chromosomal abnormalities that may involve millions of base pairs of DNA. This focus has existed largely because of technological limitations. The recent emergence of micro-array DNA technology has overcome this limitation and revealed that these intermediate-sized variants, also called genomic copy number variants (CNVs), has the potential to illuminate the contribution of genetic susceptibility to disease by a wide variety of mechanisms. The over-arching goal of this proposal is therefore to begin to determine the role that CNVs play in autism susceptibility. This will be accomplished using a DNA micro-array that brings together nearly 30,000 unique DNA elements from across the genome onto a small glass slide. The quantity of DNA at each of these elements will be tested in autistic individuals and comparison subjects. Confirmatory, low-cost assays will be developed to test these CNVs of interest in families with multiple autistic children to see whether the CNVs track with disease in those families. Significance: Data from this study will contribute to a more comprehensive understanding of the genetic basis of autism and suggest directions for future investigations.