A CCG repeat polymorphism adjacent to the CAG repeat in the Huntington disease gene: implications for diagnostic accuracy and predictive testing |
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Authors: | Andrew, Susan E. Goldberg, Y. Paul Theilmann, Jane Zeisler, Jutta Hayden, Michael R. |
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Affiliation: | Department of Medical Genetics, University of British Columbia 4162125 East Mall, Vancouver, BC V6T 1Z4, Canada |
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Abstract: | The polymorphic CAG repeat that is expanded on Huntington disease(HD) chromosomes is flanked by a CCG repeat. Here we show thatthis CCG tract, previously assumed to be invariant at sevenCCG repeats, is also polymorphic. We have identified five CCGalleles from 205 normal chromosomes, with 137 (67%) having allelesof seven repeats, five (2%) with nine repeats, 61 (30%) with10 repeats, one (0.5%) with 11 repeats and one (0.5%) with 12repeats. In contrast, analysis of 113 HD chromosomes revealedthat the majority (105 chromosomes, 93%) contained seven CCGrepeats, while the remaining eight chromosomes (7%) had allelesizes of 10 CCG repeats. Despite evidence that both CAG andCCG are polymorphic on normal chromosomes, we have found thatit is only the CAG length that has a significant impact on ageof onset. The discovery of larger sized CCG alleles, however,has significant implications for the assessment of CAG repeatlength, particularly for persons with estimated CAG size of3642 repeats, since an overestimation of CAG length inthis range could result in erroneous information being impartedto patients. |
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