No abstract available.
Spinocerebellar Ataxias* ; Trinucleotide Repeats

Numerous restraints and simplifications have been developed for methods that anticipate protein structure to reduce the colossal magnitude of possible conformational states. In this study, we investigated if globularity is a general characteristic of proteins and whether they can be applied as a valid constraint in protein structure simulations with approximated measurements (Gb-index). Unexpectedly, most of the proteins showed strong structural globularity (i.e., mode of approximately 76% similarity to the perfect globe) with only a few percent of proteins being outliers. Small proteins tended to be significantly non-globular (R2=0.79) and the minimum Gb-index showed a logarithmic increase with the increase in protein size (R2=0.62), strongly implying that the non-globular characteristics might be more acceptable for smaller proteins than larger ones. The strong perfect globe-like character and the relationship between small size and the loss of globular structure of a protein may imply that living organisms have mechanisms to aid folding into the globular structure to reduce irreversible aggregation. This also implies the possible mechanisms of diseases caused by protein aggregation, including some forms of trinucleotide repeat expansion-mediated diseases.
Protein S ; Proteins ; Trinucleotide Repeats

No abstract available.
Hantaan virus* ; RNA* ; RNA, Messenger* ; Trinucleotide Repeats*

BACKGROUND: Abnormal expansion of trinucleotide repeats in genes causing spinocerebellar ataxias such as SCA2, SCA3, SCA8, or SCA17 was reported in sporadic or familial Parkinson's disease. Genetic factors play an important role especially in early-onset Parkinson's disease (EOPD). To investigate mutations of ATXN2, ATXN3, and TBP as a possible cause in Korean EOPD, we analyzed mutations in these genes. We also investgated the possibility that trinucleotide repeats numbers in these genes contribute to the development of EOPD. METHODS: Mutation analysis of ATXN2, ATXN3, and TBP was done in 153 EOPD defined as age-at-onset before 51. Distribution of CAG repeats numbers were compared between EOPD and age- and sex-matched controls. RESULTS: No patients with EOPD had CAG repeats numbers in ATXN2, ATXN3, and TBP in mutation range. There was no difference in the distribution of CAG repeats between EOPD and controls, although we found a trend that CAG repeats numbers in ATXN3 appear larger in EOPD than in controls. CONCLUSIONS: Mutations of genes causing SCA2, SCA3, or SCA17 may not be a common genetic cause in Korean EOPD.
Humans ; Organophosphates ; Parkinson Disease ; Spinocerebellar Ataxias ; Trinucleotide Repeats

PURPOSE: Spinocerebellar ataxia (SCA) is a genetically heterogeneous disease for which more than 30 subtypes have been identified. However, 5 subtypes, SCA1, SCA2, SCA3, SCA6, and SCA7, account for more than 60% of cases. In this study, we report the distribution of these 5 subtypes in Korean patients. MATERIALS AND METHODS: Six hundred and thirty-eight unrelated patients with a presumptive diagnosis of SCA were included in this study. Trinucleotide (CAG) repeat number (TNR) repeat number was determined using fluorescently labeled primers and fragment analysis. RESULTS: A total of 128 unrelated patients (20.1% of all individuals tested) tested positive for SCA subtypes, including SCA1 (5 patients, 3.9% of those testing positive), SCA2 (38 patients, 29.7%), SCA3 (30 patients, 23.4%), SCA6 (39 patients, 30.5%), and SCA7 (16 patients, 12.5%). The mean copy number of pathogenic TNR alleles was 45+/-8.5 for SCA1, 42+/-3.1 for SCA2, 72+/-5.4 for SCA3, 23+/-1.5 for SCA6, and 50+/-11.4 for SCA7. TNR copy number was inversely correlated with onset age in SCA2, SCA6, and SCA7. CONCLUSION: SCA2, SCA3, and SCA6 are common SCA subtypes in Korean patients and could be screened as a first-line test. Expanded pathogenic allele size was associated with early onset age.
Age of Onset ; Alleles ; Diagnosis ; Humans ; Spinocerebellar Ataxias* ; Trinucleotide Repeats

BACKGROUND: The androgen receptor (AR) is a conserved member of the nuclear receptor superfamily. Differences in the AR gene sequence are characterized mostly by a highly polymorphic trinucleotide repeat (CAG) encoding a polyglutamine stretch in the N-terminal domain. The transactivational activity of the AR might be inversely associated with the numbers of this CAG repeat chain, and the smaller numbers of CAG repeats are believed to be associated with androgenetic alopecia? (AGA). OBJECTIVE: The purpose of this study was to investigate a possible etiologic association between Korean AGA and CAG repeat numbers in the AR gene. METHODS: We compared CAG repeat numbers within the AR gene of 64 male Korean AGA patients with those of 40 normal male controls. RESULTS: There was no significant difference in the number of CAG repeats between the Korean AGA patients and controls. There were no robust or significant correlations between (i) CAG repeat numbers and (ii) age of onset or severity of AGA in Korean AGA patients. CONCLUSION: This study suggests that AR receptor CAG polymorphisms in the Korean male population might not have a major role in susceptibility to AGA expression.
Age of Onset ; Alopecia ; Humans ; Male ; Peptides ; Receptors, Androgen ; Trinucleotide Repeats

BACKGROUND: The androgen receptor (AR) is a conserved member of the nuclear receptor superfamily. Differences in the AR gene sequence are characterized mostly by a highly polymorphic trinucleotide repeat (CAG) encoding a polyglutamine stretch in the N-terminal domain. The transactivational activity of the AR might be inversely associated with the numbers of this CAG repeat chain, and the smaller numbers of CAG repeats are believed to be associated with androgenetic alopecia? (AGA). OBJECTIVE: The purpose of this study was to investigate a possible etiologic association between Korean AGA and CAG repeat numbers in the AR gene. METHODS: We compared CAG repeat numbers within the AR gene of 64 male Korean AGA patients with those of 40 normal male controls. RESULTS: There was no significant difference in the number of CAG repeats between the Korean AGA patients and controls. There were no robust or significant correlations between (i) CAG repeat numbers and (ii) age of onset or severity of AGA in Korean AGA patients. CONCLUSION: This study suggests that AR receptor CAG polymorphisms in the Korean male population might not have a major role in susceptibility to AGA expression.
Age of Onset ; Alopecia ; Humans ; Male ; Peptides ; Receptors, Androgen ; Trinucleotide Repeats

A total of 12 775 SSRs were identified from Scutellaria baicalensis Georgi genomic database, accounting for 2.56% of the total genomic sequences. The result showed that S. baicalensis SSRs were based on 68.32% dinucleotide and 18.63% trinucleotide repeats; CT/GA and TTC/GAA were predominant in the dinucleotide motifs and the trinucleotide motifs respectively. Nine primers were selected to produce highly reproducible SSR bands and were used in studying the genetic diversity of S. baicalensis, 50 individuals from ten populations. 68 SSR polymorphic loci were detected, these loci were polymorphic and displayed 4 to 12 alleles per locus with a mean number of 7; the effect number of alleles was 3. Expected heterozygosities were 0.6 and were far more greater than the average in dicotyledonous plants. PIC (polymorphism information content) was 0.72, Shannon's information index was 1.32, these all proved that S. baicalensis had a high genetic diversity in general. Genetic differentiation among population Gst was 0.131, genetic variation among population accounted for 13.1% and genetic variation within population accounted for 86.9%. The cluster analysis showed that 10 populations S. Baicalensis were classified into 2 groups, but it was not associated with geographical distribution.
Alleles ; Cluster Analysis ; Genetic Variation ; Genomics ; Microsatellite Repeats ; Scutellaria baicalensis ; genetics ; Trinucleotide Repeats

Polyglutamine (Poly Q) diseases are a group of neurodegenerative disorders, caused by the formation of PolyQ mutants due to trinucleotide repeats expansion in coding regions of disease-causing genes, which eventually lead to selective neuronal degeneration and death with unclarified pathogenesis. As a new type of genetic regulatory factor, microRNA (miRNA) plays an important role in modulating gene expression in eukaryote. During the recent years, more attention was paid to roles and related mechanism of miRNA involving in neurodegenerative disease, especially PolyQ diseases. This review is focused on research progress in roles of miRNA in the pathogenesis of PolyQ diseases.
Eukaryota ; MicroRNAs ; genetics ; physiology ; Nerve Degeneration ; Neurodegenerative Diseases ; genetics ; Peptides ; genetics ; Trinucleotide Repeat Expansion ; genetics ; Trinucleotide Repeats ; genetics

BACKGROUND: Tumors are usually considered to be clonal progeny of single transformed cells. Carcinosarcomas and malignant mixed epithelial tumors are examples where controversies exist regarding the singularity or multiplicity of their cell of origin. METHODS: The authors examined the clonality of carcinosarcomas (7 cases) and malignant mixed epithelial tumor (5 cases) in female patients by X-chromosome inactivation as a marker. Each component of the tumors were picked up by the laser capture microscope. The polymorphic exon 1 CAG trinucleotide repeat in the X-linked human androgen receptor (HUMARA) gene was amplified by a polymerase chain reaction before and after treatment of the methylation-sensitive endonuclease HpaII. RESULTS: Eleven cases were informative for clonality determination. Six out of seven carcinosarcomas and three out of four malignant mixed epithelial tumors revealed the same patterns of X-chromosome inactivation, which suggests that they are monoclonal. In contrast, the patterns of X-chromosome inactivation were different between the two tumor components in each cases of carcinosarcoma and malignant mixed epithelial tumor, indicating that they are of polyclonal origin. CONCLUSIONS: These observations show that although most of carcinosarcomas and malignant mixed epithelial tumors are of monoclonal origin, some of them are of polyclonal origin. This finding suggests that these tumors are genuinely polyclonal, and that they originated in the neoplastic transformation of more than one somatic cells
Carcinosarcoma* ; Deoxyribonuclease HpaII ; Exons ; Female ; Humans ; Polymerase Chain Reaction ; Receptors, Androgen ; Trinucleotide Repeats