Abstract
Objective
To investigate the predisposing background for the instability of CAG expansions of
the HTT gene in a Chinese population.
Methods
Genotyping and haplotyping of CAG and CCG repeats of the HTT gene were carried out in 32 unrelated HD patients and 95 non-HD control individuals
of Han origin, using capillary electrophoresis and DNA sequencing. The frequencies
of different CCG repeats were compared between mutant and wild-type HTT genes. In controls, the comparison of the mean CAG repeat size was performed among
different CCG repeats.
Results
A total of five alleles of CCG repeats were distinguished, in which four were present
in HD chromosomes. In the CCG alleles, (CCG)10 showed a higher frequency in mutant
HTT genes relative to wild-type ones, and the highest mean CAG repeat size was observed
in the (CCG)10 background. Additionally, a haplotype of (CAG)32–(CCG)10 was found
in the control group.
Conclusion
Our findings indicate that HTT mutation is likely of multiple origins in the Chinese population. Among the origins,
more new HTT mutations may arise from the (CCG)10 than from other CCG alleles, which suggests
that the (CCG)10 allele may represent a predisposing background for CAG expansion
in Chinese populations. Therefore, in comparison with Europeans, the significantly
lower prevalence of Huntington's disease in Chinese individuals may not be due to
the absence of the predisposing background for CAG expansion but instead may partly
result from the lower frequency of the predisposing haplotype for CAG instability
in the population.
Keywords
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Article info
Publication history
Published online: September 28, 2010
Accepted:
August 23,
2010
Received in revised form:
August 17,
2010
Received:
January 25,
2010
Identification
Copyright
© 2010 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
