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© 1995 Oxford University Press

RESEARCH-ARTICLE

Molecular basis of p(CCG)n repeat instability at the FRA16A fragile site locus

J.K. Nancarrow, K. Holman, M. Mangelsdorf, T. Hori1, M. Denton2, G.R. Sutherland and R.I. Richards*

Centre for Medical Genetics, Department of Cytogenetics and Molecular Genetics, Women's and Children's Hospital North Adelaide, SA 5006, Australia 1Division of Genetics, National Institute of Radiological Sciences Chiba, Japan 2Department of Biochemistry, University of Otago Otago, New Zealand

*To whom correspondence should be addressed

Received October 21, 1994; Revised December 12, 1994; Accepted December 12, 1994

Rare, folate-sensitive fragile sites are the result of the unstable expansion of trinucleotide p(CCG)n repeats, which are normally polymorphic in copy number. Differences in the number and frequency of alleles of the fragile site FRA16A p(CCG)n repeat were observed between different ethnic populations suggesting that certain alleles might be predisposed to instability. Sequence analysis demonstrated that the longer and more variable alleles were associated with loss of repeat interruption. Perfect repeat configuration therefore appears to be a necessary precondition for the instability associated with fragile site genesis.


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