Skip Navigation

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (22)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Rodenhiser, D. I.
Right arrow Articles by Singh, S. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rodenhiser, D. I.
Right arrow Articles by Singh, S. M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 1993 Oxford University Press

OTHER

Evidence of DNA methylation in the neurofibromatosis type 1 (NF1) gene region of 17q11.2

David I. Rodenhiser1,2,*, Marion B. Coulter-Mackie1,2,3,5 and Shiva M. Singh1,2,4

1Child Health Research Institute, Children's Hospital of Western Ontario London, Ontario, N6C 2V5 2Departments of Paediatrics, University of Western Ontario London, Ontario N6H 3W7, Canada 3Departments of Biochemistry, University of Western Ontario London, Ontario N6H 3W7, Canada 4Departments of Zoology, University of Western Ontario London, Ontario N6A 5B7 5Children's Psychiatric Research Institute London, Ontario N6H 3W7, Canada

*Molecular Medical Genetics Laboratory, A4 WT, Child Health Research Institute, Children's Hospital of Western Ontario, 800 Commissioner's Road East, London, Ontario N6C 2V5, Canada

Received November 10, 1992; Revised February 1, 1993; Accepted February 1, 1993

Modification of mammalian DNA by the methylation of cytosine in CpG dinucleotides is a complex phenomenon involved in a number of cellular and developmental processes. In a particular, the characteristic hypermutability of CpGs may be a major contributor of point mutations leading to human genetic disease. We have hypothesized that DNA methylation contributes to mutations in the gene causing neurofibromatosis type 1 (NF1), one of the most common genetic disorders in humans and a disease where up to half of all cases are the result of sporadic germline mutations, usually in the paternally-derived allele. We have used two experimental approaches to analyze patterns of DNA methylation at CpG dinucleotides in the NF1 gene region. Southern analyses using isoschizomeric restriction pairs have revealed DNA methylation in areas flanking the NF1 gene region, while PCR-methylation assays have shown that methylation occurs both on genomic sequences flanking the NF1 gene and within the coding region of the gene itself. We suggest that methylated CpG dinucleotides within and around the highly mutable NF1 gene serve as a reservoir within which C-T transitions contribute to the high frequency of spontaneous germline mutations associated with the disease.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Hum Mol GenetHome page
J. L. Rutkowski, K. Wu, D. H. Gutmann, P. J. Boyer, and E. Legius
Genetic and cellular defects contributing to benign tumor formation in neurofibromatosis type 1
Hum. Mol. Genet., April 12, 2000; 9(7): 1059 - 1066.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
O. Levran, T. Erlich, N. Magdalena, J. J. Gregory, S. D. Batish, P. C. Verlander, and A. D. Auerbach
Sequence variation in the Fanconi anemia gene FAA
PNAS, November 25, 1997; 94(24): 13051 - 13056.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.