Evidence for a predisposing background for CAG expansion leading to HTT mutation in a Chinese population.
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.


CONCLUSIONS
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.
Ma
Mingyi
M
Department of Medical Genetics, West China Hospital and State Key Laboratory of Biotherapy, Sichuan University, Gaopeng street, Keyuan Road 4, Chengdu, Sichuan 610041, China.
Yang
Yuan
Y
Shang
Huifang
H
Su
Dan
D
Zhang
Hao
H
Ma
Yongxin
Y
Liu
Yunqiang
Y
Tao
Dachang
D
Zhang
Sizhong
S
D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics; D002681:China / Q000453:epidemiology; D004247:DNA / Q000235:genetics; D019075:Electrophoresis, Capillary; D005260:Female; D018628:Gene Dosage; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000453:epidemiology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics* / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*
C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D004247:DNA