Abstract for presentation at 11th International Congress of Human Genetics

Using High Resolution Genomic Microarrays to Study Chromosomal Aberrations and DNA Methylation Patterns in Autism

  • Simon Gregory, Duke University Center for Human Genetics, United States
  • Dr Jessica Connelly, Duke University Center for Human Genetics, United States
  • Dr G Delong, Department of Pediatric Neurology, Duke University Medical Center, United States
  • Dr Ruth Abramson, Department of Neuropsychiatry, University of South Carolina, United States
  • Dr Harold Wright, Department of Neuropsychiatry, University of South Carolina, United States
  • Dr Michael DeLong, Duke University Center for Human Genetics, United States
  • Dr Jeffery Vance, Duke University Center for Human Genetics, United States
  • Dr Margaret Pericak-Vance, Duke University Center for Human Genetics, United States

    • Autistic disorder (AutD) is highly heritable, with a relative risk for siblings of 50-100 times that of the general population. Multiple studies have identified a number of genomic linkage regions, but a gene associated with AutD has yet to be identified. Additional studies have suggested that genetic changes, such as chromosome aberrations, contribute to at least 5% of individuals with idiopathic AutD. Recent reports that mutations in methyl CpG binding protein 2 (MECP2) can also lead to AutD. These data suggests that chromosome rearrangements and changes in DNA methylation could be responsible for this disorder. Previous studies investigating genomic rearrangements or aberrant methylation profiles in AutD have only investigated focused genomic regions.
    We have performed genome wide copy number analysis of 130 probands with idiopathic AutD by high resolution comparative genomic hybridization (hrCGH) using a tilepath microarray of 50kb resolution. Results from our hrCGH analysis were compared within our AutD patient dataset and also to the genomic profiles of 80 phenotypically normal individuals. This allows us to identify genomic mutations which are unique to individuals with AutD but to also determine if there is an association of normal copy number polymorphism to the AutD phenotype, thus elucidating the genetic for AutD development. Analysis of arrayCGH data for 130 individuals has identified 166 regions (> 1 tilepath clone) of genomic rearrangement contained within 3 or more individuals. 50 regions contain known normal CNPs and 116 are novel regions of genomic rearrangement. Within the total 166 regions, 7 are contained within previously published linkage peaks. We are using recently published techniques to isolate, label and analyze differentially methylated regions of the genome within 10 AutD and unaffected individuals using our tilepath microarray. We present the results of our ongoing methylation analysis, and its integration with the AutD hrCGH data.

    Conference Organiser - ICMS Pty Ltd