Abstract for presentation at 11th International Congress of Human Genetics

High resolution characterization of recurrent copy number variation

  • Dr Stefan White, Leiden University Medical Center, The Netherlands
  • L E L M Vissers, Radboud University Nijmegen Medical Center, The Netherlands
  • Geurts van Kessell, Radboud University Nijmegen Medical Center, The Netherlands
  • M H Breuning, Leiden University Medical Center, The Netherlands
  • Dr Han Brunner, Radboud University Nijmegen Medical Center, The Netherlands
  • Joris Veltman, Radboud University Nijmegen Medical Center, The Netherlands
  • J T den Dunnen, Leiden University Medical Center, The Netherlands
  • Gertjan van Ommen, Leiden University Medical Center, The Netherlands

    • Recent studies have revealed a new type of genetic variation encompassing relatively large genomic segments (~100 kb - 2.2 Mb), referred to as copy number variation (CNV). With this field still in its infancy, there is relatively little known about the origin, extent and frequency of CNV. We have begun to explore these questions using high-resolution, high throughput techniques such as MAPH and MLPA.
    In an attempt to gain insight into which sequences, structures and/or processes are involved in the generation of de novo CNV, we have summarized rearrangements detected in the DMD gene of ~3000 Duchenne / Becker Muscular Dystrophy patients. The deletion and duplication profile across the gene will be discussed, along with the information that has been collected regarding the possible causes of these rearrangements.
    We have also used MLPA to determine the frequencies of recurrent CNV in 12 genomic regions recently detected by array CGH. More than 300 individuals from five different ethnic populations, including three distinct European, one Asian and one African population, were tested for the occurrence of CNV using at least two specific MLPA probes per region. Seven of these regions showed CNV in all populations, including the ß-defensin gene cluster (8p23.1), the TBC1D3 region (17q12), and (part of) the NSF gene (17q21.31). For the duplicated part of the NSF locus, ~70% of individuals showed copy numbers different from the median, with estimated copy numbers varying between 2 and 7. Furthermore, we detected different copy number distributions between populations, suggesting that this locus is under selective pressure. Future studies will be aimed at the effect of recurrent CNV on gene expression levels and their potential involvement in human health and disease.

    Conference Organiser - ICMS Pty Ltd