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

Mingyi Ma1, Yuan Yang, Huifang Shang

  • 1Department of Medical Genetics, West China Hospital and State Key Laboratory of Biotherapy, Sichuan University, Gaopeng street, Keyuan Road 4, Chengdu, Sichuan 610041, China.

Journal of the Neurological Sciences
|September 25, 2010
PubMed

Insights

The (CCG)10 allele in the HTT gene may predispose Chinese populations to Huntington's disease (HD) by increasing CAG repeat instability. This finding suggests a genetic basis for HD prevalence differences between Chinese and European populations.

Area of Science:

  • Genetics
  • Human Molecular Genetics
  • Population Genetics

Background:

  • Huntington's disease (HD) is caused by CAG repeat expansions in the HTT gene.
  • The instability of these CAG repeats is influenced by flanking sequences, such as CCG repeats.
  • Understanding the genetic background of CAG repeat instability is crucial for explaining population-specific HD prevalence.

Purpose of the Study:

  • To investigate the predisposing genetic background for CAG repeat instability of the HTT gene in a Chinese population.
  • To compare the frequencies of CCG repeat alleles between HD patients and controls.
  • To identify specific CCG repeat alleles or haplotypes associated with increased CAG expansion.

Main Methods:

  • Genotyping and haplotyping of CAG and CCG repeats in the HTT gene were performed using capillary electrophoresis and DNA sequencing.
  • The study included 32 unrelated HD patients and 95 non-HD controls of Han Chinese origin.
  • Frequencies of CCG repeats and mean CAG repeat sizes were compared between mutant and wild-type HTT genes and across different CCG repeat backgrounds.

Main Results:

  • Five CCG repeat alleles were identified, with four found in HD chromosomes.
  • (CCG)10 showed a higher frequency in mutant HTT genes compared to wild-type genes.
  • The highest mean CAG repeat size was observed in individuals with the (CCG)10 background, and a (CAG)32-(CCG)10 haplotype was identified in controls.

Conclusions:

  • HTT mutations likely have multiple origins in the Chinese population.
  • The (CCG)10 allele may represent a predisposing background for CAG expansion in Chinese populations, potentially leading to new HTT mutations.
  • Lower HD prevalence in Chinese compared to Europeans may be due to a lower frequency of predisposing haplotypes for CAG instability, not an absence of such backgrounds.
Abstract

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