Molecular Analysis of the Huntington’s Disease with Expanded CAG Trinucleotide Repeat in Chinese

The polymorphic CAG repeats in the IT15 gene in Chinese normal and Huntington’s dis-ease(HD)chromosomes were determined by using nested PCR and denaturing polyacry-lamide gel electrophoretic autoradiography as well as direct sequencing analysis.A total of40 normal individuals and 122 members of 13 unrelated HD families originating from Shang-hai,Jiangsu,Zhejiang,Anhui,Shandong,Guangdong and Henan,respectively,were in-volved in this study.The results showed that the(CAG)n repeat numbers in 270 normal al-leles ranged from 13 to 26 but most in 16;while in 54 HD alleles,the CAG repeats from 40to 94,with an unstable inheritance of expanded repeats in some families.There was no over-lap between the normal and affected alleles.Additionally,the presymptomatic diagnosis in103 family members at risk for HD disclosed that 35 individuals had HD alleles,which were-in accordance with the pedigree analysis and clinical investigation.All these results indicatedthat the dynamic mutation in IT15 gene was responsible for the genetic defect in the ChineseHD patients and that a correlation existed between the numbers of(CAG)n repeat and theonset age of the disease.All-of these provide valuable data for HD molecular diagnosis,ge-netic counselling and genetic health.