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Biomedical subjects

J G Chang

Publications and source records attributed to J G Chang.

At least 37 records · Page 2Linked to original sources
PubMed2000

Mutation analysis of the putative tumor suppressor gene PTEN/MMAC1 in cervical cancer.

OBJECTIVE: PTEN/MMAC1, a candidate tumor suppressor gene located at chromosome 10q23.3, was recently identified and found to be homozygously deleted or mutated in several different types of human tumors. The aim of this study is to determine whether PTEN/MMAC1 is a target for 10q loss of heterozygosity in cervical cancer. METHOD: We examined 50 primary cervical carcinoma specimens using a PCR-based assay followed by SSCP and direct sequencing. The genomic DNA was also confirmed by Southern blot analysis. RESULTS: All specimens except one, which has a 7-base deletion, showed a negative result. Among them, 30 randomly selected cases and their paired noncancerous tissue were further screened using nested RT-PCR. Six of 30 cervical cancerous tissues had aberrant transcripts. However, 4 of the matched noncancerous tissues also had aberrant transcripts. Southern blot analysis of the entire genomic DNA did not reveal any evidence of gene alteration. CONCLUSIONS: Sequence abnormalities in the PTEN/MMAC1 gene were only detected in 1 of 50 cervical cancers analyzed indicating that aberrant PTEN/MMAC1 function is an uncommon event in the development of cervix cancers. However, similar to studies with the TSG101 gene, screening for aberrant transcripts of PTEN/MMAC1 with nested RT-PCR may detect transcripts, which, although they vary from the normal size, may not be related to oncogenesis as they are also frequently found in normal tissues of the same patient.

Adult↗
PubMed2000

Lewis (FUT3) genotypes in Taiwanese, Thai, and Filipino populations.

The Lewis (Le) blood type comprises two major antigens, Le(a) and Le(b), which are encoded by alpha (1,2)-fucosyltransferase (FUT2) and a (1,3/1,4)-fucosyl-transferase (FUT3). In this study, we analyzed the mutations of FUT3 in Taiwanese, Thai, and Filipino populations and correlated these with serologic phenotypes. One hundred and thirty-seven Taiwanese, 71 Thai, and 125 Filipino were studied unselectively. The frequency of the normal and four other mutant alleles for Taiwanese, Thai, and Filipino, respectively, were as follows: 187/274 (68.2%), 87/142 (61.3%), and 160/250 (64.0%) were wild type (Le); 14/274 (5.1%), 1/142 (0.7%), and 1/250 (0.4%) were a T202C/C314T mutation (le202,314); 35/274 (12.8%), 15/142 (10.6%), and 22/250 (8.8%) had the G508A mutation (le508); and 38/274 (13.9%), 39/142 (27.4%), and 67/250 (26.8%) carried the T1067A mutation (le1067). The le445 and le1007 were not detected in this study. Our result provided the first genetic data of the FUT3 gene in these three populations, and the frequency distribution of mutant alleles among Taiwanese, Thai, and Filipinos demonstrates a significant difference (P<0.001). In our study, the le202,314 mutation had considerable frequency in the Taiwanese, but the le1067 mutation had a higher frequency in Thai and Filipinos.

Adult↗
PubMed2000

A mouse model for spinal muscular atrophy.

The survival motor neuron gene is present in humans in a telomeric copy, SMN1, and several centromeric copies, SMN2. Homozygous mutation of SMN1 is associated with proximal spinal muscular atrophy (SMA), a severe motor neuron disease characterized by early childhood onset of progressive muscle weakness. To understand the functional role of SMN1 in SMA, we produced mouse lines deficient for mouse Smn and transgenic mouse lines that expressed human SMN2. Smn-/- mice died during the peri-implantation stage. In contrast, transgenic mice harbouring SMN2 in the Smn-/- background showed pathological changes in the spinal cord and skeletal muscles similar to those of SMA patients. The severity of the pathological changes in these mice correlated with the amount of SMN protein that contained the region encoded by exon 7. Our results demonstrate that SMN2 can partially compensate for lack of SMN1. The variable phenotypes of Smn-/-SMN2 mice reflect those seen in SMA patients, providing a mouse model for this disease.

Animals↗
PubMed2000

Association of CTLA4 gene A-G polymorphism with type 1 diabetes in Chinese children.

OBJECTIVE: The CTLA4 (cytotoxic T lymphocyte associated antigen-4) gene encodes the T cell receptor involved in the control of T cell proliferation and mediates T cell apoptosis. Thus it is a strong candidate gene for T cell-mediated autoimmune disease. There is polymorphism at position 49 in exon 1 of the CTLA4 gene, providing a A-G exchange. This polymorphism is reportedly associated with type 1 diabetes in Caucasians but not in a small data set of Chinese. We wished to test this polymorphism in a larger and more homogeneous data set of Chinese children with type 1 diabetes and normal adult controls. DESIGN: A population-based case-control study of a CTLA4 gene 49 A-G polymorphism was performed to look for an association with type 1 diabetes in Chinese children. PATIENTS: We analysed this polymorphism in 253 unrelated children (128 boys) with type 1 diabetes (age at diagnosis 7.1 +/- 3.7 years) and 91 randomly selected normal adults. All individuals were Han Chinese. RESULTS: The genotype and gene frequencies of children with type 1 diabetes differed significantly from those of adult controls (P = 0.0091 and P = 0.0051, respectively). Genotype CTLA4 49 G/G and G allele conferred a risk of type 1 diabetes (RR = 2.13, 95% CI = 1.31-3.46, P = 0.0022; RR = 1.68, 95% CI = 1.17-2.43, P = 0.0051, respectively). CONCLUSIONS: This study demonstrates that CTLA4 49 A-G polymorphism is associated with type 1 diabetes in Han Chinese children. The CTLA4 49 G allele confers an increased risk of type 1 diabetes.

Abatacept↗
PubMed2000

Genomic typing of human red cell miltenberger glycophorins in a Taiwanese population.

BACKGROUND: Antigens in the human red cell Miltenberger series are glycophorin variants of the MN (MNS) blood group system that are due to the rearrangement of glycophorin A (GPA) and glycophorin B (GPB) genes. STUDY DESIGN AND METHODS: Taking advantage of the differences between the GPA and GPB genes, a polymerase chain reaction-based method was developed to detect all the Miltenberger glycophorin variants and St(a) subtype. GPA- and GPB-specific primers were used to amplify the GPA or GPB gene, and the amplified products were used to recognize the different hybrid genes after restriction enzyme digestions. RESULTS: Among 264 Taiwanese subjects studied, Mi.III and St(a) are the most common types of Miltenberger variants found. Mi.III was present in 13 (4.92%) of 264, and St(a) was found in 8 (3. 03%) of 264; 1 case (0.4%) of Mi.V was also identified from the study group. CONCLUSION: This is the first polymerase chain reaction-based method of detecting most of the Miltenberger variants and St(a). The genomic typing results were confirmed by control DNA of identified Miltenberger phenotypes. The prevalence rates of Mi. III and St(a) in this study were also consistent with other previous reports using different methods.

Erythrocytes↗
PubMed2000

Polymorphisms of the parkin gene in sporadic Parkinson's disease among Chinese in Taiwan.

The role of genetics in Parkinson's disease (PD), previously controversial, is now documented by several studies. A major breakthrough has been the discovery of two single-gene defects in familial PD. A single base pair change at position 209 from G to A (G209A) in the fourth exon of the alpha-synuclein gene has been identified in cases of autosomal dominant familial PD. Mutations in the Parkin gene can induce autosomal recessive juvenile parkinsonism. A polymorphism of R/W366 in the Parkin gene was found to be associated with a protective factor for sporadic PD. We surveyed the polymorphisms of the Parkin gene, including S/N167, R/W366 and V/L380, in 92 cases of sporadic PD and 98 nonaffected individuals in Taiwanese Chinese. The allele frequencies of these polymorphisms are not significantly different between PD and nonaffected controls. We conclude that polymorphisms of the Parkin gene, S/N167, R/W366, V/L380, are not genetic factors for sporadic PD among Chinese in Taiwan.

Aged↗
PubMed2000

Polymorphism of transmembrane region of MICA gene and Kawasaki disease.

Kawasaki disease is a febrile disease of children complicated with vasculitis of the coronary arteries and potential aneurysm formation. It has been recognized worldwide and appears to be increasing in frequency. Studies have found that Kawasaki disease is associated with major histocompatibility complex (MHC) class I B antigens. The MHC-class-I-chain-related gene A (MICA) is located near HLA-B. It has a triplet repeat microsatellite polymorphism in the transmembrane region. We investigated the microsatellite polymorphism in children with Kawasaki disease and controls. Seventy children (46 boys), age at diagnosis 1.68 +/- 1.69 years, with Kawasaki who were treated with aspirin as well as intravenous gamma-globulin were enrolled. Control subjects consisted of 154 children (87 boys), age 2.81 +/- 2.12 years. Phenotype frequency of allele A4 in patients with aneurysm formation was significantly lower than in patients without aneurysms [relative risk (RR) = 0.06, 95% confidence interval (CI) = 0.01-0.48, p = 0.00469, pc = 0.0232] and showed a similar tendency when compared with controls. Gene frequency of allele A4 was also significantly lower in patients who developed aneurysms than in patients who did not (RR = 0.07, 95% CI = 0.01-0.57, p = 0.0057, pc = 0.0282). Gene frequency of allele A5 showed a tendency to be higher in patients who developed aneurysms than in controls (RR = 2.35, 95% CI = 0.98-5.63, p = 0.0486, pc = 0. 220). Allele A5.1 tended to be negatively associated with Kawasaki disease (RR = 0.57, 95% CI = 0.35-0.93, p = 0.022, pc = 0.105). Our study showed that allele A4 was negatively associated with coronary aneurysm formation in Kawasaki disease. This suggests that allele A4 protects the children with Kawasaki disease from developing coronary aneurysms after aspirin and gamma globulin therapy.

Alleles↗
PubMed2000

Carrier analysis and prenatal diagnosis of congenital adrenal hyperplasia caused by 21-hydroxylase deficiency in Chinese.

Congenital adrenal hyperplasia (CAH) is a common autosomal recessive disorder mainly caused by defects in the steroid 21-hydroxylase (CYP21) gene. We screened 1,000 healthy people, using a previously developed differential PCR method combined with single-strand conformation polymorphism and amplification-created restriction site methods for the carrier detection of the CYP21 gene deficiency. Our results indicated that the rate of occurrence of the heterozygous CAH carrier was about 12 in 1,000, with a gene frequency of 0.0060 and an incidence frequency of 1 in 28,000 in the Chinese population. In addition, 9 cases of CAH families were performed with prenatal diagnosis. Among them, 3 cases were diagnosed as the severe form, 4 cases carried the heterozygous mutation, and 2 were normal. This is the first report of carrier frequency analysis and prenatal diagnosis of 21-hydroxylase deficiency in Chinese.

Adrenal Hyperplasia, Congenital↗
PubMed2000

Polymorphism in the transmembrane region of the MICA gene and type 1 diabetes.

Although MHC class II genes have a stronger association with type 1 diabetes than MHC class I genes, studies have shown that MHC class I molecules play an independent role in the etiology of type 1 diabetes, and the existence of susceptibility genes within a segment of MHC between the HLA-B and TNF genes has been predicted, where MHC class I chain-related gene A (MICA) resides. MICA has a triplet repeat polymorphism in the transmembrane region consisting of five alleles. We analyzed this polymorphism in 162 unrelated children (82 boys) with type 1 diabetes (age at diagnosis 7.01 +/- 3.76 yr) and 154 randomly selected unrelated children (87 boys), age 2.81 +/- 2.12 yr. Phenotype frequency of allele A9 in children with type 1 diabetes was significantly higher than in controls (RR = 2.42, 95% CI = 1.52-3.85, p = 0.000162, pc = 0.00081). Gene frequency of allele A9 was also significantly higher in children with type 1 diabetes when compared with control children (RR = 2.73, 95% CI = 1.85-4.03, p = 2.62 x 10(-7), pc = 1.31 x 10(-6)). This study demonstrates that MICA allele A9 confers risk of type 1 diabetes.

Alleles↗
PubMed2000

Mutation analysis of the putative tumor suppressor gene PTEN/MMAC1 in hepatocellular carcinoma.

Loss of heterozygosity of chromosome 10q has been reported in hepatoma. Areas with a high rate of loss of genetic material could harbor putative tumor suppressor genes. PTEN/MMAC1, a candidate tumor suppressor gene located at chromosome 10q23.3, has recently been identified and found to be homozygously deleted or mutated in several different types of human tumors. To determine whether the PTEN/MMAC1 gene is a target of 10q loss of heterozygosity in hepatoma, we examined 42 primary hepatomas for mutations in PTEN/MMAC1 by using nested reverse transcriptase polymerase chain reaction (RT-PCR) of the RNA and single-stranded conformation polymorphism (SSCP) analysis of all genomic exons. Although 2 of 42 hepatoma tissues had aberrant transcripts, 5 matched noncancerous liver tissues also had aberrant transcripts. Southern blot analysis of the entire genomic DNA revealed no genomic change. Therefore, like the TSG101 or FHIT gene, aberrant transcripts of PTEN/MMAC1 using the nested RT-PCR method were a common phenomenon for both cancerous and noncancerous liver tissues, which may not be related to oncogenesis. None of the 42 cases had small deletions, point mutations, or insertions. Our results suggest that the PTEN/MMAC1 gene may not play a role in the pathogenesis of hepatoma.

Blotting, Southern↗
PubMed2000

Clinical implications of aberrant TSG101 transcripts in acute myeloblastic leukemia.

Tsg101 is a mouse tumor suppressor gene whose homozygous deletion produces transformation of NIH3T3 cells and leads to metastases in nude mice. The human homologue of the gene, TSG101, is localized in chromosome 11p15.1-p15.2. Reduced TSG101 expression may cause the defect of the cell cycle checkpoint that leads to genetic instability and consequently to the progression of neoplasia. Aberrant TSG101 transcript have been identified in many types of cancers, and the relaxation of RNA splicing fidelity may be an onco-developmental marker in cancers and could play a general role in tumorigenesis. In our previous study, smaller TSG101 transcripts were found in AML specimens, hematopoietic cell lines and normal controls. The aberrant transcripts occurred more frequently in the AML cases and cell lines. The patients with aberrant TSG101 transcripts had higher initial white cell count, lower LDH level, and lower complete remission rate after induction chemotherapy. However, further multivariate analysis of clinical data revealed that there was no relationship to the TSG101 aberrant transcripts. The clinical significance of TSG101 aberrant transcript in AML needs further evaluation.

3T3 Cells↗
PubMed2000

Aberrant transcripts of FHIT, TSG101 and PTEN/MMAC1 genes in normal peripheral mononuclear cells.

Aberrant transcripts of FHIT and TSG101 using nested RT-PCR were reported in many human tumours. The role of these aberrant transcripts in tumourigenesis is not clear. We, therefore, analyzed the aberrant transcripts of FHIT, TSG101 and PTEN/MMAC1 in peripheral mononuclear cells of normal individuals using nested RT-PCR to explore the role of these genes in cancer development. The results showed that there are at least five types of aberrant transcripts: type I is the deletion at junction located in-between normal exon and intron; type II has deletion of some bases and subsequent insertion of several bases in the deletion area; type III accommodates splicing donor or acceptor site-like sequence; type IV has homologous sequences near the deleted junction; and type V comprises the homologous sequences at the deletion junction. A normal healthy person can have more than one aberrant transcripts of FHIT, TSG101 and PTEN/MMAC1 genes. The size and the number of the transcripts vary and the diversity is unconstrained. It is not depended on the time, condition of the reaction, or the isolation method. From these results, we suggested that the aberrant transcripts of FHIT, TSG101 and PTEN/MMAC1 genes may be the imperfect products of splicesome which occur one in every thousands, ten thousands or more. As a result, these data implied no direct association between the aberrant transcripts and tumourigenesis.

Acid Anhydride Hydrolases↗
PubMed2000

Mutation analysis of PTEN/MMAC 1 in sporadic thyroid tumors.

Recently, a putative tumor suppressor gene, PTEN/MMAC1, has been identified at chromosome 10q23.3. This gene encodes a 403 amino acid dual specificity phosphatase containing a region of homology to tensin and auxillin. Somatic mutations of the PTEN/MMAC1 gene have been found in a number of cancer cell lines and primary cancers. Cowden disease, an autosomal dominant harmartoma syndrome associated with thyroid and breast tumors, has been found to be associated with mutations of PTEN/MMAC1 gene. To evaluate the role of the PTEN/MMAC1 gene in sporadic thyroid tumors, we studied 17 sporadic thyroid tumors, of which 12 were papillary thyroid carcinomas, 1 was follicular thyroid carcinoma, 1 was medullary thyroid carcinoma and 3 were thyroid adenomas. Direct sequencing of PCR-amplified products was performed for all nine exons of PTEN/MMAC1. No mutations of PTEN/MMAC1 gene were observed in any of the sporadic thyroid tumors. Our results indicate that the PTEN/MMAC1 gene may not play a major role in sporadic thyroid tumors.

Genes, Tumor Suppressor↗
PubMed2000

Analysis of the chimeric CYP21P/CYP21 gene in steroid 21-hydroxylase deficiency.

BACKGROUND: A single nonfunctional chimeric gene with its 5' and 3' ends corresponding to CYP21P and CYP21, respectively, is caused by unequal gene crossover in the CYP21 genes during meiosis. The presence of the chimeric CYP21P/CYP21 molecule can not be detected by conventional PCR methods and therefore may be lost in PCR amplification. This leads to a false result and diagnostic discordance. METHODS: We developed a rapid and direct method to detect a chimeric CYP21P/CYP21 gene that uses a 3'-specific primer for the CYP21 gene and two different 5' primers for both CYP21 and CYP21P to amplify the wild-type CYP21 and the chimeric CYP21P/CYP21 genes. A secondary PCR that can differentiate the chimeric from the wild-type gene was also performed. The PCR product was directly analyzed on agarose gel. RESULTS: After careful titration, we found that earlier failure to detect the chimeric CYP21P/CYP21 gene could be caused by unequal concentrations of two independent alleles as the PCR template or by the lack of primers to amplify chimeric molecules. We successfully amplified the chimeric gene using our improved method. CONCLUSIONS: The chimeric CYP21P/CYP21 is present in a large portion of congenital adrenal hyperplasia patients. By adding a CYP21P/CYP21-specific primer, we were able to amplify and detect both homozygous and heterozygous chimeric genes. Therefore, our new PCR-based assay is a more effective way to analyze congenital adrenal hyperplasia mutations.

Adrenal Hyperplasia, Congenital↗
PubMed2000

Molecular analysis of Duffy, Yt and Colton blood groups in Taiwanese, Filipinos and Thais.

We used a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method for DNA-based typing of Duffy, Yt and Colton blood groups in Taiwanese, Filipinos and Thais. A total of 200 Taiwanese, 115 Filipinos and 105 Thais were studied. In the Duffy blood group in Taiwanese, 180 cases (90%) were homozygote of Fya, 18 cases (9%) were double heterozygote of Fya and Fyb, and 2 cases (1%) were homozygote of Fyb. In Filipinos, 98 cases (85.2%) were homozygote of Fya, 16 cases (14.0%) were double heterozygote of Fya and Fyb and 1 case (0.8%) was homozygote of Fyb. In Thais, 87 cases (82.9%) were homozygote of Fya, 18 cases (17.1%) were double heterozygote of Fya and Fyb, and no case of Fyb was found. These results correlate well with serological phenotype. For the Yt blood group, only YT1 was found in Taiwanese. Among Filipinos, 114/115 (99.1%) was YT1/1 and 1/115 (0.9%) was YT1/2. In Thais, 103/105 (98.1%) was YT1/1 and 2/105 (1.9%) was YT1/2. For the Colton blood group, the results showed that there was only Coa allele in these three populations. Our results provide the first data of the Yt and Colton blood groups in these three populations.

Blood Group Antigens↗
PubMed2000

Analysis of an SMN gene-like DNA fragment.

Part of a survival motor neuron (SMN) gene-like DNA fragment has been identified. This DNA fragment was accidentally isolated from cDNA by RT-PCR using primers specific for the region between exon 3 and 6 of the SMN gene. This fragment was used as a probe to hybridize the mRNA from several tissues, but we have been unable to detect any transcript of this SMN-like gene in these tissues. Thus, we have inferred this SMN gene-like fragment was a genomic product contaminant that was amplified in the reaction. Sequencing analysis of this fragment, which contains several stop codons, revealed a 74.6% nucleotide homology with the SMN gene. From these results, we believe that this DNA fragment is not a mutated form of SMN gene. Rather, it is an SMN-like pseudogene, which is variably present even in normal individuals.

Base Sequence↗
PubMed2000

Mutation analysis of the Bcl 10 gene in hepatocellular carcinoma.

The Bcl 10 gene was recently discovered to be involved in the pathogenesis of lymphoma of mucosa-associated lymphoid tissue and several types of tumorous cell lines. We examined the mutation of Bcl 10 gene in 31 hepatocellular carcinomas along with their corresponding non-tumorous tissues by single strand conformation polymorphism (SSCP) and direct sequencing. The results showed that 11.3% chromosomes had codon 5 GCA to TCA mutation, 4.8% chromosomes had codon 8 CTC to CTG mutation, and 12.9% chromosomes had codon 213 GGA to GAA mutation. These mutations were found not only in the hepatoma tissues but also in paired non-cancerous tissues and the normal population. We suggest that these three changes are polymorphisms, and there is no relationship with the development of hepatocellular carcinoma.

Adaptor Proteins, Signal Transducing↗