Clinical and Molecular Consequences of NF1 Microdeletion
Annual rept. 7 Apr 2005-6 Apr 2006
SEATTLE UNIV WA
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We have developed rapid and sensitive assays for the detection and mapping of both the common 1.4 Mb NF1 microdeletion and novel microdeletions clinical evaluation of these patients will help to delineate the common clinical manifestations of this patient group. Our hypothesis that genome instability occurs during NF1-tumorigenesis was supported by 2 findings. First, we describe a novel mechanism of somatic NF1 loss in NF1-related leukemias, which add to our understanding of leukemogenesis and identifies chromsomal regions were somatic recombination may be favored. Second, we localized neurofibromin to the centrosome in at least some cells, which along with our preliminary observations that centrosomes appear abnormal in NF1-related neurofibromas, implicates neurofibromin in normal centrosome function and in maintaining genome stability. Our detailed analysis of human and chimpanzee genome sequences were consistent with the presence of a single NF1 gene copy, which adds a new level of evidence to existing chromosomal and physical data reputing a prior report of tandem NF1 genes.
- Genetic Engineering and Molecular Biology
- Anatomy and Physiology
- Medicine and Medical Research