On Conjugation Partitions of Sets of Trinucleotides

We prove that a trinucleotide circular code is self-complementary if and only if its two conjugated classes are complement of each other. Using only this proposition, we prove that if a circular code is self-complementary then either both its two conjugated classes are circular codes or none is a circular code.

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.

Clinical Characteristics, Radiological Features and Gene Mutation in 10 Chinese Families with Spinocerebellar Ataxias

Background： Spinocerebellar ata^ias （SCAs） are a group ofneurodegenerative disorders that primarily cause the degeneration in the cerebellum, spinal cord, and brainstem. We study the clinical characteristics, radiological features and gene mutation in Chinese families with SCAs. Methods： In this study, we investigated 10 SCAs Chinese families with SCAI, SCA3/Machado-Joseph disease （MJD}, SCA7, SCAB. There were 27 people who were genetically diagnosed as SCA, of which 21 people showed clinical symptoms, and 6 people had no clinical phenotype that we called them presymptomatic patients. In addition, 3 people with cerebellar ataxia and cataracts were diagnosed according to the Harding diagnostic criteria but tailed to be recognized as SCAs on genetic testing. Clinical characteristic analyses of each type of SCAs and radiological examinations were perlbrmed. Results： We found that SCA3/MJD was the most common subtype in Hart population in China, and the ratio of the pontine tegmentum and the posterior fossa area was negatively con＇elated with the number of cytosine-adenine-guanine （CAG） repeats： the disease duration was positively correlated with the International Cooperative Ataxia Rating Scale score; and the CAG repeats number of abnormal alleles was negatively correlated with the age of onset. Conchlsions： Collectively our study is a systematic research on SCAs in China, which may help for the clinical diagnosis and prenatal screening of this disease, and it may also aid toward better understanding of this disease.

Frequency analysis of autosomal dominant spinocerebellar ataxias in mainland Chinese patients and clinical and molecular characterization of spinocerebellar ataxia type 6

Background Dominantly inherited spinocerebellar ataxia (SCA) is a clinically and genetically heterogeneous group of neurodegenerative disorders. This study was to further assess the frequency of SCA1 (spinocerebellar ataxia type 1), SCA2, SCA3/MJD (spinocerebellar ataxia type 3/Machado-Joseph disease), SCA6, SCA7, SCA8, SCA10, SCA12, SCA14, SCA17 and DRPLA (dentatorubro-pallidoluysian atrophy) in mainland Chinese, and to specifically characterize mainland Chinese patients with SCA6 in terms of clinical and molecular features.Methods Using a molecular approach, we investigated SCA in 120 mainland Chinese families with dominantly inherited ataxias and in 60 mainland Chinese patients with sporadic ataxias. Clinical and molecular features of SCA6 were further characterized in 13 patients from 4 families. Results SCA3/MJD was the most common type of autosomal dominant SCA in mainland Chinese, accounting for 83 patients from 59 families (49.2%), followed by SCA2[8(6.7%)], SCA1[7(5.8%)], SCA6[4(3.3%)], SCA7[1(0.8%)], SCA8(0%), SCA10(0%), SCA12(0%), SCA14(0%), SCA17(0%) and DRPLA(0%). The genes responsible for 41 (34.2%) of dominantly inherited SCA families remain to be determined. Among the 60 patients with sporadic ataxias in the present series, 3 (5.0%) was found to harbor SCA3 mutations while none was found to harbor SCA6 mutations. In the 4 families with SCA6, significant anticipation was found in the absence of genetic instability on transmission.Conclusion A geographic cluster of families with SCA6 subtype was initially identified in a mainland Chinese population.

DNA mismatch repair in trinucleotide repeat instability

Trinucleotide repeat expansions cause over 30 severe neuromuscular and neurodegenerative disorders, including Huntington's disease, myotonic dystrophy type 1, and fragile X syndrome. Although previous studies have substantially advanced the understanding of the disease biology, many key features remain unknown. DNA mismatch repair(MMR) plays a critical role in genome maintenance by removing DNA mismatches generated during DNA replication. However, MMR components,particularly mismatch recognition protein MutSβ and its interacting factors MutLα and MutLγ, have been implicated in trinucleotide repeat instability. In this review, we will discuss the roles of these key MMR proteins in promoting trinucleotide repeat instability.