Di Qiao | University of Illinois at Chicago (original) (raw)

Papers by Di Qiao

Research paper thumbnail of Promoter polymorphism of matrilin-1 gene predisposes to adolescent idiopathic scoliosis in a Chinese population

European Journal of Human Genetics, 2009

Adolescent idiopathic scoliosis (AIS) is widely recognized as a complex disorder with a strong ge... more Adolescent idiopathic scoliosis (AIS) is widely recognized as a complex disorder with a strong genetic predisposition. In previous studies, a number of extracellular matrixes (ECMs) related genes have been duplicated as candidate genes for AIS. Matrilin-1 plays an important role in the organization of the ECM, and matrilin-1 gene (MATN1) mutant mice showed similar phenotypes to scoliosis. We hypothesized that MATN1 was a candidate predisposition gene for AIS. A gene-based association study was conducted using seven tagging SNPs identified from the HapMap data. For initial screening, the seven tagSNPs were genotyped in 197 cases and 172 controls. Next, we validated any significant association in an additional sample of 222 cases and 288 controls. In addition, another 290 controls were genotyped to confirm the results. We found that allele G of rs1149048 was a significant predisposition allele of AIS (P ¼ 0.0007, odds ratio (OR) ¼ 1.35 within 95% confidence interval (CI) ¼ 1.14 -1.61), and individuals with genotype GG had a higher risk for AIS compared with AA þ AG (P ¼ 0.0001, OR ¼ 1.61 within 95% CI ¼ 1.25-2.08). Polymorphism of rs1149048 was also associated with curve severity in AIS patients. Also, a significantly higher maximum Cobb angle was found in patients with GG genotype (P ¼ 0.002). We concluded that the tagSNP rs1149048 polymorphism in the MATN1 promoter region was associated with both susceptibility and disease progression in AIS.

Research paper thumbnail of Replication of the association of the aspartic acid repeat polymorphism in the asporin gene with knee-osteoarthritis susceptibility in Han Chinese

Journal of Human Genetics, 2006

A genetic association of osteoarthritis (OA) and functional polymorphisms in the aspartic acid (D... more A genetic association of osteoarthritis (OA) and functional polymorphisms in the aspartic acid (D) repeat of the asporin gene was reported in Japanese and European Caucasians; however, the results were controversial. Our objective was to evaluate whether the D repeat polymorphism was associated with knee OA in Han Chinese. The D repeat polymorphism was genotyped in 218 patients who suffered from primary symptomatic knee OA with radiographic confirmation and in 454 age-matched controls, and the allelic association of the repeat was examined. Frequencies of the D13 and D14 alleles were similar to those of Japanese, but different from those of European Caucasians. The D14 allele was significantly over-represented in knee OA patients (P=0.0013; odds ratio 2.04; 95% confidence interval 1.32–3.15). D14 was more frequent in early-onset patients than in late-onset patients (P=0.043) and the age at onset in patients with D14 was earlier (P=0.028; log-rank test). Thus, the association of the D14 allele with knee OA susceptibility was replicated in Han Chinese. This was the first instance that association of the OA susceptibility gene was definitely replicated between different ethnic groups.

Research paper thumbnail of VEGF C−634G polymorphism is associated with protection from isolated ventricular septal defect: case–control and TDT studies

European Journal of Human Genetics, 2007

The ventricular septal defect (VSD) is the most common congenital heart defect and no candidate s... more The ventricular septal defect (VSD) is the most common congenital heart defect and no candidate susceptibility gene has been identified. Endocardial cushion and outflow septal morphogenesis, malalignment of which induces VSD, have been suggested to be mediated by the vascular endothelial growth factor (VEGF). Three single-nucleotide polymorphism (SNP) variants in promoter and 5'-UTR region of the VEGF gene, C-2578A (rs699947), G-1154A (rs1570360) and G-634C (rs2010963), were reported to alter its expression. We assessed the association in a Chinese population between these SNPs and VSD using a double approach: case-control and TDT designs. Among the three SNPs, only -634C allele was less frequently present in 222 patients compared to 352 controls (odds ratio: 0.76, 95% CI: 0.59-0.97, X(2)=5.06, P=0.024, not significant after a Bonferroni correction). This was significantly less transmitted to VSD patients (trios: 142) (odds ratio: 0.39, 95% CI: 0.25-0.62, X(2)=8.11, df=1, P=0.004, corrected P=0.024). A similar result was observed for haplotype -2578C/-1154G/-634C allele in both studies (in TDT: X(2)=7.51, df=1, P=0.006, corrected P=0.048). All these associations for the first time demonstrated that -634C allele was in a significant protective association against VSD, suggesting that VEGF dysregulation was involved in the pathological processes of VSD.

Research paper thumbnail of Cystic fibrosis transmembrane conductance regulator (CFTR) gene 5T allele may protect against prostate cancer: A case-control study in Chinese Han population

Journal of Cystic Fibrosis, 2008

The cystic fibrosis transmembrane conductance regulator (CFTR) is a Cl − channel that governs the... more The cystic fibrosis transmembrane conductance regulator (CFTR) is a Cl − channel that governs the quantity and composition of epithelial secretions. CFTR function is normally tightly controlled as dysregulation can lead to lifethreatening diseases such as secretory diarrhoea and cystic fibrosis. CFTR activity is regulated by phosphorylation of its cytosolic regulatory (R) domain, and ATP binding and hydrolysis at two nucleotide-binding domains (NBDs). Here, we report that CFTR activity is also controlled by extracellular Cl − concentration ([Cl − ] o ). Patch clamp current recordings show that a rise in [Cl − ] o stimulates CFTR channel activity, an effect conferred by a single arginine residue, R899, in extracellular loop 4 of the protein. Using NBD mutants and ATP dose response studies in WT channels, we determined that [Cl − ] o sensing was linked to changes in ATP binding energy at NBD1, which likely impacts NBD dimer stability. Biochemical measurements showed that increasing [Cl − ] o decreased the intrinsic ATPase activity of CFTR mainly through a reduction in maximal ATP turnover. Our studies indicate that sensing [Cl − ] o is a novel mechanism for regulating CFTR activity and suggest that the luminal ionic environment is an important physiological arbiter of CFTR function, which has significant implications for salt and fluid homeostasis in epithelial tissues.

Research paper thumbnail of A novel competitive fluorescent multiplex STR polymorphism assay for rapid, reliable and single-tube screening of 22q11.2 copy-number aberrations

Electrophoresis, 2009

Copy-number aberrations of the 22q11.2 region can lead to varied resulting and complex phenotypes... more Copy-number aberrations of the 22q11.2 region can lead to varied resulting and complex phenotypes. Routine screening for these common constitutional chromosomal abnormalities requires powerful tools. A competitive fluorescent multiplex STR polymorphism assay (CFMSA) was built for detecting these aberrations. With the introduction of an internal reference and distinguishable STR polymorphism markers, this competitive fluorescent multiplex STR polymorphism assay provides complementary information about polymorphism and gene dosage in one tube simultaneously, thereby enhancing the assay sensitivity. It was first tested in 110 normal controls, and was proven to have highly polymorphic and reliable gene dosage information. Then, 476 subjects with congenital heart defect were screened according to the testing strategy of the American Heart Association, and 17 deletions and 1 duplication of 22q11.2 were correctly identified. It is expected that this assay will serve as a cost-effective alternative to existing assays for routine, large-scale screening in all at-risk individuals with either deletion or duplication in 22q11.2.

Research paper thumbnail of Promoter polymorphism of matrilin-1 gene predisposes to adolescent idiopathic scoliosis in a Chinese population

European Journal of Human Genetics, 2009

Adolescent idiopathic scoliosis (AIS) is widely recognized as a complex disorder with a strong ge... more Adolescent idiopathic scoliosis (AIS) is widely recognized as a complex disorder with a strong genetic predisposition. In previous studies, a number of extracellular matrixes (ECMs) related genes have been duplicated as candidate genes for AIS. Matrilin-1 plays an important role in the organization of the ECM, and matrilin-1 gene (MATN1) mutant mice showed similar phenotypes to scoliosis. We hypothesized that MATN1 was a candidate predisposition gene for AIS. A gene-based association study was conducted using seven tagging SNPs identified from the HapMap data. For initial screening, the seven tagSNPs were genotyped in 197 cases and 172 controls. Next, we validated any significant association in an additional sample of 222 cases and 288 controls. In addition, another 290 controls were genotyped to confirm the results. We found that allele G of rs1149048 was a significant predisposition allele of AIS (P ¼ 0.0007, odds ratio (OR) ¼ 1.35 within 95% confidence interval (CI) ¼ 1.14 -1.61), and individuals with genotype GG had a higher risk for AIS compared with AA þ AG (P ¼ 0.0001, OR ¼ 1.61 within 95% CI ¼ 1.25-2.08). Polymorphism of rs1149048 was also associated with curve severity in AIS patients. Also, a significantly higher maximum Cobb angle was found in patients with GG genotype (P ¼ 0.002). We concluded that the tagSNP rs1149048 polymorphism in the MATN1 promoter region was associated with both susceptibility and disease progression in AIS.

Research paper thumbnail of Replication of the association of the aspartic acid repeat polymorphism in the asporin gene with knee-osteoarthritis susceptibility in Han Chinese

Journal of Human Genetics, 2006

A genetic association of osteoarthritis (OA) and functional polymorphisms in the aspartic acid (D... more A genetic association of osteoarthritis (OA) and functional polymorphisms in the aspartic acid (D) repeat of the asporin gene was reported in Japanese and European Caucasians; however, the results were controversial. Our objective was to evaluate whether the D repeat polymorphism was associated with knee OA in Han Chinese. The D repeat polymorphism was genotyped in 218 patients who suffered from primary symptomatic knee OA with radiographic confirmation and in 454 age-matched controls, and the allelic association of the repeat was examined. Frequencies of the D13 and D14 alleles were similar to those of Japanese, but different from those of European Caucasians. The D14 allele was significantly over-represented in knee OA patients (P=0.0013; odds ratio 2.04; 95% confidence interval 1.32–3.15). D14 was more frequent in early-onset patients than in late-onset patients (P=0.043) and the age at onset in patients with D14 was earlier (P=0.028; log-rank test). Thus, the association of the D14 allele with knee OA susceptibility was replicated in Han Chinese. This was the first instance that association of the OA susceptibility gene was definitely replicated between different ethnic groups.

Research paper thumbnail of VEGF C−634G polymorphism is associated with protection from isolated ventricular septal defect: case–control and TDT studies

European Journal of Human Genetics, 2007

The ventricular septal defect (VSD) is the most common congenital heart defect and no candidate s... more The ventricular septal defect (VSD) is the most common congenital heart defect and no candidate susceptibility gene has been identified. Endocardial cushion and outflow septal morphogenesis, malalignment of which induces VSD, have been suggested to be mediated by the vascular endothelial growth factor (VEGF). Three single-nucleotide polymorphism (SNP) variants in promoter and 5'-UTR region of the VEGF gene, C-2578A (rs699947), G-1154A (rs1570360) and G-634C (rs2010963), were reported to alter its expression. We assessed the association in a Chinese population between these SNPs and VSD using a double approach: case-control and TDT designs. Among the three SNPs, only -634C allele was less frequently present in 222 patients compared to 352 controls (odds ratio: 0.76, 95% CI: 0.59-0.97, X(2)=5.06, P=0.024, not significant after a Bonferroni correction). This was significantly less transmitted to VSD patients (trios: 142) (odds ratio: 0.39, 95% CI: 0.25-0.62, X(2)=8.11, df=1, P=0.004, corrected P=0.024). A similar result was observed for haplotype -2578C/-1154G/-634C allele in both studies (in TDT: X(2)=7.51, df=1, P=0.006, corrected P=0.048). All these associations for the first time demonstrated that -634C allele was in a significant protective association against VSD, suggesting that VEGF dysregulation was involved in the pathological processes of VSD.

Research paper thumbnail of Cystic fibrosis transmembrane conductance regulator (CFTR) gene 5T allele may protect against prostate cancer: A case-control study in Chinese Han population

Journal of Cystic Fibrosis, 2008

Cystic fibrosis (CF) is caused by defects in the CF transmembrane conductance regulator (CFTR) th... more Cystic fibrosis (CF) is caused by defects in the CF transmembrane conductance regulator (CFTR) that functions as a chloride channel in epithelial cells. The most common cause of CF is the abnormal trafficking of CFTR mutants. Therefore, understanding the cellular ...

Research paper thumbnail of A novel competitive fluorescent multiplex STR polymorphism assay for rapid, reliable and single-tube screening of 22q11.2 copy-number aberrations

Electrophoresis, 2009

Copy-number aberrations of the 22q11.2 region can lead to varied resulting and complex phenotypes... more Copy-number aberrations of the 22q11.2 region can lead to varied resulting and complex phenotypes. Routine screening for these common constitutional chromosomal abnormalities requires powerful tools. A competitive fluorescent multiplex STR polymorphism assay (CFMSA) was built for detecting these aberrations. With the introduction of an internal reference and distinguishable STR polymorphism markers, this competitive fluorescent multiplex STR polymorphism assay provides complementary information about polymorphism and gene dosage in one tube simultaneously, thereby enhancing the assay sensitivity. It was first tested in 110 normal controls, and was proven to have highly polymorphic and reliable gene dosage information. Then, 476 subjects with congenital heart defect were screened according to the testing strategy of the American Heart Association, and 17 deletions and 1 duplication of 22q11.2 were correctly identified. It is expected that this assay will serve as a cost-effective alternative to existing assays for routine, large-scale screening in all at-risk individuals with either deletion or duplication in 22q11.2.

Research paper thumbnail of Promoter polymorphism of matrilin-1 gene predisposes to adolescent idiopathic scoliosis in a Chinese population

European Journal of Human Genetics, 2009

Adolescent idiopathic scoliosis (AIS) is widely recognized as a complex disorder with a strong ge... more Adolescent idiopathic scoliosis (AIS) is widely recognized as a complex disorder with a strong genetic predisposition. In previous studies, a number of extracellular matrixes (ECMs) related genes have been duplicated as candidate genes for AIS. Matrilin-1 plays an important role in the organization of the ECM, and matrilin-1 gene (MATN1) mutant mice showed similar phenotypes to scoliosis. We hypothesized that MATN1 was a candidate predisposition gene for AIS. A gene-based association study was conducted using seven tagging SNPs identified from the HapMap data. For initial screening, the seven tagSNPs were genotyped in 197 cases and 172 controls. Next, we validated any significant association in an additional sample of 222 cases and 288 controls. In addition, another 290 controls were genotyped to confirm the results. We found that allele G of rs1149048 was a significant predisposition allele of AIS (P ¼ 0.0007, odds ratio (OR) ¼ 1.35 within 95% confidence interval (CI) ¼ 1.14 -1.61), and individuals with genotype GG had a higher risk for AIS compared with AA þ AG (P ¼ 0.0001, OR ¼ 1.61 within 95% CI ¼ 1.25-2.08). Polymorphism of rs1149048 was also associated with curve severity in AIS patients. Also, a significantly higher maximum Cobb angle was found in patients with GG genotype (P ¼ 0.002). We concluded that the tagSNP rs1149048 polymorphism in the MATN1 promoter region was associated with both susceptibility and disease progression in AIS.

Research paper thumbnail of Replication of the association of the aspartic acid repeat polymorphism in the asporin gene with knee-osteoarthritis susceptibility in Han Chinese

Journal of Human Genetics, 2006

A genetic association of osteoarthritis (OA) and functional polymorphisms in the aspartic acid (D... more A genetic association of osteoarthritis (OA) and functional polymorphisms in the aspartic acid (D) repeat of the asporin gene was reported in Japanese and European Caucasians; however, the results were controversial. Our objective was to evaluate whether the D repeat polymorphism was associated with knee OA in Han Chinese. The D repeat polymorphism was genotyped in 218 patients who suffered from primary symptomatic knee OA with radiographic confirmation and in 454 age-matched controls, and the allelic association of the repeat was examined. Frequencies of the D13 and D14 alleles were similar to those of Japanese, but different from those of European Caucasians. The D14 allele was significantly over-represented in knee OA patients (P=0.0013; odds ratio 2.04; 95% confidence interval 1.32–3.15). D14 was more frequent in early-onset patients than in late-onset patients (P=0.043) and the age at onset in patients with D14 was earlier (P=0.028; log-rank test). Thus, the association of the D14 allele with knee OA susceptibility was replicated in Han Chinese. This was the first instance that association of the OA susceptibility gene was definitely replicated between different ethnic groups.

Research paper thumbnail of VEGF C−634G polymorphism is associated with protection from isolated ventricular septal defect: case–control and TDT studies

European Journal of Human Genetics, 2007

The ventricular septal defect (VSD) is the most common congenital heart defect and no candidate s... more The ventricular septal defect (VSD) is the most common congenital heart defect and no candidate susceptibility gene has been identified. Endocardial cushion and outflow septal morphogenesis, malalignment of which induces VSD, have been suggested to be mediated by the vascular endothelial growth factor (VEGF). Three single-nucleotide polymorphism (SNP) variants in promoter and 5'-UTR region of the VEGF gene, C-2578A (rs699947), G-1154A (rs1570360) and G-634C (rs2010963), were reported to alter its expression. We assessed the association in a Chinese population between these SNPs and VSD using a double approach: case-control and TDT designs. Among the three SNPs, only -634C allele was less frequently present in 222 patients compared to 352 controls (odds ratio: 0.76, 95% CI: 0.59-0.97, X(2)=5.06, P=0.024, not significant after a Bonferroni correction). This was significantly less transmitted to VSD patients (trios: 142) (odds ratio: 0.39, 95% CI: 0.25-0.62, X(2)=8.11, df=1, P=0.004, corrected P=0.024). A similar result was observed for haplotype -2578C/-1154G/-634C allele in both studies (in TDT: X(2)=7.51, df=1, P=0.006, corrected P=0.048). All these associations for the first time demonstrated that -634C allele was in a significant protective association against VSD, suggesting that VEGF dysregulation was involved in the pathological processes of VSD.

Research paper thumbnail of Cystic fibrosis transmembrane conductance regulator (CFTR) gene 5T allele may protect against prostate cancer: A case-control study in Chinese Han population

Journal of Cystic Fibrosis, 2008

Cystic fibrosis (CF) is caused by defects in the CF transmembrane conductance regulator (CFTR) th... more Cystic fibrosis (CF) is caused by defects in the CF transmembrane conductance regulator (CFTR) that functions as a chloride channel in epithelial cells. The most common cause of CF is the abnormal trafficking of CFTR mutants. Therefore, understanding the cellular ...

Research paper thumbnail of A novel competitive fluorescent multiplex STR polymorphism assay for rapid, reliable and single-tube screening of 22q11.2 copy-number aberrations

Electrophoresis, 2009

Copy-number aberrations of the 22q11.2 region can lead to varied resulting and complex phenotypes... more Copy-number aberrations of the 22q11.2 region can lead to varied resulting and complex phenotypes. Routine screening for these common constitutional chromosomal abnormalities requires powerful tools. A competitive fluorescent multiplex STR polymorphism assay (CFMSA) was built for detecting these aberrations. With the introduction of an internal reference and distinguishable STR polymorphism markers, this competitive fluorescent multiplex STR polymorphism assay provides complementary information about polymorphism and gene dosage in one tube simultaneously, thereby enhancing the assay sensitivity. It was first tested in 110 normal controls, and was proven to have highly polymorphic and reliable gene dosage information. Then, 476 subjects with congenital heart defect were screened according to the testing strategy of the American Heart Association, and 17 deletions and 1 duplication of 22q11.2 were correctly identified. It is expected that this assay will serve as a cost-effective alternative to existing assays for routine, large-scale screening in all at-risk individuals with either deletion or duplication in 22q11.2.

Research paper thumbnail of Promoter polymorphism of matrilin-1 gene predisposes to adolescent idiopathic scoliosis in a Chinese population

European Journal of Human Genetics, 2009

Adolescent idiopathic scoliosis (AIS) is widely recognized as a complex disorder with a strong ge... more Adolescent idiopathic scoliosis (AIS) is widely recognized as a complex disorder with a strong genetic predisposition. In previous studies, a number of extracellular matrixes (ECMs) related genes have been duplicated as candidate genes for AIS. Matrilin-1 plays an important role in the organization of the ECM, and matrilin-1 gene (MATN1) mutant mice showed similar phenotypes to scoliosis. We hypothesized that MATN1 was a candidate predisposition gene for AIS. A gene-based association study was conducted using seven tagging SNPs identified from the HapMap data. For initial screening, the seven tagSNPs were genotyped in 197 cases and 172 controls. Next, we validated any significant association in an additional sample of 222 cases and 288 controls. In addition, another 290 controls were genotyped to confirm the results. We found that allele G of rs1149048 was a significant predisposition allele of AIS (P ¼ 0.0007, odds ratio (OR) ¼ 1.35 within 95% confidence interval (CI) ¼ 1.14 -1.61), and individuals with genotype GG had a higher risk for AIS compared with AA þ AG (P ¼ 0.0001, OR ¼ 1.61 within 95% CI ¼ 1.25-2.08). Polymorphism of rs1149048 was also associated with curve severity in AIS patients. Also, a significantly higher maximum Cobb angle was found in patients with GG genotype (P ¼ 0.002). We concluded that the tagSNP rs1149048 polymorphism in the MATN1 promoter region was associated with both susceptibility and disease progression in AIS.

Research paper thumbnail of Replication of the association of the aspartic acid repeat polymorphism in the asporin gene with knee-osteoarthritis susceptibility in Han Chinese

Journal of Human Genetics, 2006

A genetic association of osteoarthritis (OA) and functional polymorphisms in the aspartic acid (D... more A genetic association of osteoarthritis (OA) and functional polymorphisms in the aspartic acid (D) repeat of the asporin gene was reported in Japanese and European Caucasians; however, the results were controversial. Our objective was to evaluate whether the D repeat polymorphism was associated with knee OA in Han Chinese. The D repeat polymorphism was genotyped in 218 patients who suffered from primary symptomatic knee OA with radiographic confirmation and in 454 age-matched controls, and the allelic association of the repeat was examined. Frequencies of the D13 and D14 alleles were similar to those of Japanese, but different from those of European Caucasians. The D14 allele was significantly over-represented in knee OA patients (P=0.0013; odds ratio 2.04; 95% confidence interval 1.32–3.15). D14 was more frequent in early-onset patients than in late-onset patients (P=0.043) and the age at onset in patients with D14 was earlier (P=0.028; log-rank test). Thus, the association of the D14 allele with knee OA susceptibility was replicated in Han Chinese. This was the first instance that association of the OA susceptibility gene was definitely replicated between different ethnic groups.

Research paper thumbnail of VEGF C−634G polymorphism is associated with protection from isolated ventricular septal defect: case–control and TDT studies

European Journal of Human Genetics, 2007

The ventricular septal defect (VSD) is the most common congenital heart defect and no candidate s... more The ventricular septal defect (VSD) is the most common congenital heart defect and no candidate susceptibility gene has been identified. Endocardial cushion and outflow septal morphogenesis, malalignment of which induces VSD, have been suggested to be mediated by the vascular endothelial growth factor (VEGF). Three single-nucleotide polymorphism (SNP) variants in promoter and 5'-UTR region of the VEGF gene, C-2578A (rs699947), G-1154A (rs1570360) and G-634C (rs2010963), were reported to alter its expression. We assessed the association in a Chinese population between these SNPs and VSD using a double approach: case-control and TDT designs. Among the three SNPs, only -634C allele was less frequently present in 222 patients compared to 352 controls (odds ratio: 0.76, 95% CI: 0.59-0.97, X(2)=5.06, P=0.024, not significant after a Bonferroni correction). This was significantly less transmitted to VSD patients (trios: 142) (odds ratio: 0.39, 95% CI: 0.25-0.62, X(2)=8.11, df=1, P=0.004, corrected P=0.024). A similar result was observed for haplotype -2578C/-1154G/-634C allele in both studies (in TDT: X(2)=7.51, df=1, P=0.006, corrected P=0.048). All these associations for the first time demonstrated that -634C allele was in a significant protective association against VSD, suggesting that VEGF dysregulation was involved in the pathological processes of VSD.

Research paper thumbnail of Cystic fibrosis transmembrane conductance regulator (CFTR) gene 5T allele may protect against prostate cancer: A case-control study in Chinese Han population

Journal of Cystic Fibrosis, 2008

Cystic fibrosis (CF) is caused by defects in the CF transmembrane conductance regulator (CFTR) th... more Cystic fibrosis (CF) is caused by defects in the CF transmembrane conductance regulator (CFTR) that functions as a chloride channel in epithelial cells. The most common cause of CF is the abnormal trafficking of CFTR mutants. Therefore, understanding the cellular ...

Research paper thumbnail of A novel competitive fluorescent multiplex STR polymorphism assay for rapid, reliable and single-tube screening of 22q11.2 copy-number aberrations

Electrophoresis, 2009

Copy-number aberrations of the 22q11.2 region can lead to varied resulting and complex phenotypes... more Copy-number aberrations of the 22q11.2 region can lead to varied resulting and complex phenotypes. Routine screening for these common constitutional chromosomal abnormalities requires powerful tools. A competitive fluorescent multiplex STR polymorphism assay (CFMSA) was built for detecting these aberrations. With the introduction of an internal reference and distinguishable STR polymorphism markers, this competitive fluorescent multiplex STR polymorphism assay provides complementary information about polymorphism and gene dosage in one tube simultaneously, thereby enhancing the assay sensitivity. It was first tested in 110 normal controls, and was proven to have highly polymorphic and reliable gene dosage information. Then, 476 subjects with congenital heart defect were screened according to the testing strategy of the American Heart Association, and 17 deletions and 1 duplication of 22q11.2 were correctly identified. It is expected that this assay will serve as a cost-effective alternative to existing assays for routine, large-scale screening in all at-risk individuals with either deletion or duplication in 22q11.2.

Research paper thumbnail of Promoter polymorphism of matrilin-1 gene predisposes to adolescent idiopathic scoliosis in a Chinese population

European Journal of Human Genetics, 2009

Adolescent idiopathic scoliosis (AIS) is widely recognized as a complex disorder with a strong ge... more Adolescent idiopathic scoliosis (AIS) is widely recognized as a complex disorder with a strong genetic predisposition. In previous studies, a number of extracellular matrixes (ECMs) related genes have been duplicated as candidate genes for AIS. Matrilin-1 plays an important role in the organization of the ECM, and matrilin-1 gene (MATN1) mutant mice showed similar phenotypes to scoliosis. We hypothesized that MATN1 was a candidate predisposition gene for AIS. A gene-based association study was conducted using seven tagging SNPs identified from the HapMap data. For initial screening, the seven tagSNPs were genotyped in 197 cases and 172 controls. Next, we validated any significant association in an additional sample of 222 cases and 288 controls. In addition, another 290 controls were genotyped to confirm the results. We found that allele G of rs1149048 was a significant predisposition allele of AIS (P ¼ 0.0007, odds ratio (OR) ¼ 1.35 within 95% confidence interval (CI) ¼ 1.14 -1.61), and individuals with genotype GG had a higher risk for AIS compared with AA þ AG (P ¼ 0.0001, OR ¼ 1.61 within 95% CI ¼ 1.25-2.08). Polymorphism of rs1149048 was also associated with curve severity in AIS patients. Also, a significantly higher maximum Cobb angle was found in patients with GG genotype (P ¼ 0.002). We concluded that the tagSNP rs1149048 polymorphism in the MATN1 promoter region was associated with both susceptibility and disease progression in AIS.

Research paper thumbnail of Replication of the association of the aspartic acid repeat polymorphism in the asporin gene with knee-osteoarthritis susceptibility in Han Chinese

Journal of Human Genetics, 2006

A genetic association of osteoarthritis (OA) and functional polymorphisms in the aspartic acid (D... more A genetic association of osteoarthritis (OA) and functional polymorphisms in the aspartic acid (D) repeat of the asporin gene was reported in Japanese and European Caucasians; however, the results were controversial. Our objective was to evaluate whether the D repeat polymorphism was associated with knee OA in Han Chinese. The D repeat polymorphism was genotyped in 218 patients who suffered from primary symptomatic knee OA with radiographic confirmation and in 454 age-matched controls, and the allelic association of the repeat was examined. Frequencies of the D13 and D14 alleles were similar to those of Japanese, but different from those of European Caucasians. The D14 allele was significantly over-represented in knee OA patients (P=0.0013; odds ratio 2.04; 95% confidence interval 1.32–3.15). D14 was more frequent in early-onset patients than in late-onset patients (P=0.043) and the age at onset in patients with D14 was earlier (P=0.028; log-rank test). Thus, the association of the D14 allele with knee OA susceptibility was replicated in Han Chinese. This was the first instance that association of the OA susceptibility gene was definitely replicated between different ethnic groups.

Research paper thumbnail of VEGF C−634G polymorphism is associated with protection from isolated ventricular septal defect: case–control and TDT studies

European Journal of Human Genetics, 2007

The ventricular septal defect (VSD) is the most common congenital heart defect and no candidate s... more The ventricular septal defect (VSD) is the most common congenital heart defect and no candidate susceptibility gene has been identified. Endocardial cushion and outflow septal morphogenesis, malalignment of which induces VSD, have been suggested to be mediated by the vascular endothelial growth factor (VEGF). Three single-nucleotide polymorphism (SNP) variants in promoter and 5'-UTR region of the VEGF gene, C-2578A (rs699947), G-1154A (rs1570360) and G-634C (rs2010963), were reported to alter its expression. We assessed the association in a Chinese population between these SNPs and VSD using a double approach: case-control and TDT designs. Among the three SNPs, only -634C allele was less frequently present in 222 patients compared to 352 controls (odds ratio: 0.76, 95% CI: 0.59-0.97, X(2)=5.06, P=0.024, not significant after a Bonferroni correction). This was significantly less transmitted to VSD patients (trios: 142) (odds ratio: 0.39, 95% CI: 0.25-0.62, X(2)=8.11, df=1, P=0.004, corrected P=0.024). A similar result was observed for haplotype -2578C/-1154G/-634C allele in both studies (in TDT: X(2)=7.51, df=1, P=0.006, corrected P=0.048). All these associations for the first time demonstrated that -634C allele was in a significant protective association against VSD, suggesting that VEGF dysregulation was involved in the pathological processes of VSD.

Research paper thumbnail of Cystic fibrosis transmembrane conductance regulator (CFTR) gene 5T allele may protect against prostate cancer: A case-control study in Chinese Han population

Journal of Cystic Fibrosis, 2008

The cystic fibrosis transmembrane conductance regulator (CFTR) is a Cl − channel that governs the... more The cystic fibrosis transmembrane conductance regulator (CFTR) is a Cl − channel that governs the quantity and composition of epithelial secretions. CFTR function is normally tightly controlled as dysregulation can lead to lifethreatening diseases such as secretory diarrhoea and cystic fibrosis. CFTR activity is regulated by phosphorylation of its cytosolic regulatory (R) domain, and ATP binding and hydrolysis at two nucleotide-binding domains (NBDs). Here, we report that CFTR activity is also controlled by extracellular Cl − concentration ([Cl − ] o ). Patch clamp current recordings show that a rise in [Cl − ] o stimulates CFTR channel activity, an effect conferred by a single arginine residue, R899, in extracellular loop 4 of the protein. Using NBD mutants and ATP dose response studies in WT channels, we determined that [Cl − ] o sensing was linked to changes in ATP binding energy at NBD1, which likely impacts NBD dimer stability. Biochemical measurements showed that increasing [Cl − ] o decreased the intrinsic ATPase activity of CFTR mainly through a reduction in maximal ATP turnover. Our studies indicate that sensing [Cl − ] o is a novel mechanism for regulating CFTR activity and suggest that the luminal ionic environment is an important physiological arbiter of CFTR function, which has significant implications for salt and fluid homeostasis in epithelial tissues.

Research paper thumbnail of A novel competitive fluorescent multiplex STR polymorphism assay for rapid, reliable and single-tube screening of 22q11.2 copy-number aberrations

Electrophoresis, 2009

Copy-number aberrations of the 22q11.2 region can lead to varied resulting and complex phenotypes... more Copy-number aberrations of the 22q11.2 region can lead to varied resulting and complex phenotypes. Routine screening for these common constitutional chromosomal abnormalities requires powerful tools. A competitive fluorescent multiplex STR polymorphism assay (CFMSA) was built for detecting these aberrations. With the introduction of an internal reference and distinguishable STR polymorphism markers, this competitive fluorescent multiplex STR polymorphism assay provides complementary information about polymorphism and gene dosage in one tube simultaneously, thereby enhancing the assay sensitivity. It was first tested in 110 normal controls, and was proven to have highly polymorphic and reliable gene dosage information. Then, 476 subjects with congenital heart defect were screened according to the testing strategy of the American Heart Association, and 17 deletions and 1 duplication of 22q11.2 were correctly identified. It is expected that this assay will serve as a cost-effective alternative to existing assays for routine, large-scale screening in all at-risk individuals with either deletion or duplication in 22q11.2.

Research paper thumbnail of Promoter polymorphism of matrilin-1 gene predisposes to adolescent idiopathic scoliosis in a Chinese population

European Journal of Human Genetics, 2009

Adolescent idiopathic scoliosis (AIS) is widely recognized as a complex disorder with a strong ge... more Adolescent idiopathic scoliosis (AIS) is widely recognized as a complex disorder with a strong genetic predisposition. In previous studies, a number of extracellular matrixes (ECMs) related genes have been duplicated as candidate genes for AIS. Matrilin-1 plays an important role in the organization of the ECM, and matrilin-1 gene (MATN1) mutant mice showed similar phenotypes to scoliosis. We hypothesized that MATN1 was a candidate predisposition gene for AIS. A gene-based association study was conducted using seven tagging SNPs identified from the HapMap data. For initial screening, the seven tagSNPs were genotyped in 197 cases and 172 controls. Next, we validated any significant association in an additional sample of 222 cases and 288 controls. In addition, another 290 controls were genotyped to confirm the results. We found that allele G of rs1149048 was a significant predisposition allele of AIS (P ¼ 0.0007, odds ratio (OR) ¼ 1.35 within 95% confidence interval (CI) ¼ 1.14 -1.61), and individuals with genotype GG had a higher risk for AIS compared with AA þ AG (P ¼ 0.0001, OR ¼ 1.61 within 95% CI ¼ 1.25-2.08). Polymorphism of rs1149048 was also associated with curve severity in AIS patients. Also, a significantly higher maximum Cobb angle was found in patients with GG genotype (P ¼ 0.002). We concluded that the tagSNP rs1149048 polymorphism in the MATN1 promoter region was associated with both susceptibility and disease progression in AIS.

Research paper thumbnail of Replication of the association of the aspartic acid repeat polymorphism in the asporin gene with knee-osteoarthritis susceptibility in Han Chinese

Journal of Human Genetics, 2006

A genetic association of osteoarthritis (OA) and functional polymorphisms in the aspartic acid (D... more A genetic association of osteoarthritis (OA) and functional polymorphisms in the aspartic acid (D) repeat of the asporin gene was reported in Japanese and European Caucasians; however, the results were controversial. Our objective was to evaluate whether the D repeat polymorphism was associated with knee OA in Han Chinese. The D repeat polymorphism was genotyped in 218 patients who suffered from primary symptomatic knee OA with radiographic confirmation and in 454 age-matched controls, and the allelic association of the repeat was examined. Frequencies of the D13 and D14 alleles were similar to those of Japanese, but different from those of European Caucasians. The D14 allele was significantly over-represented in knee OA patients (P=0.0013; odds ratio 2.04; 95% confidence interval 1.32–3.15). D14 was more frequent in early-onset patients than in late-onset patients (P=0.043) and the age at onset in patients with D14 was earlier (P=0.028; log-rank test). Thus, the association of the D14 allele with knee OA susceptibility was replicated in Han Chinese. This was the first instance that association of the OA susceptibility gene was definitely replicated between different ethnic groups.

Research paper thumbnail of VEGF C−634G polymorphism is associated with protection from isolated ventricular septal defect: case–control and TDT studies

European Journal of Human Genetics, 2007

The ventricular septal defect (VSD) is the most common congenital heart defect and no candidate s... more The ventricular septal defect (VSD) is the most common congenital heart defect and no candidate susceptibility gene has been identified. Endocardial cushion and outflow septal morphogenesis, malalignment of which induces VSD, have been suggested to be mediated by the vascular endothelial growth factor (VEGF). Three single-nucleotide polymorphism (SNP) variants in promoter and 5'-UTR region of the VEGF gene, C-2578A (rs699947), G-1154A (rs1570360) and G-634C (rs2010963), were reported to alter its expression. We assessed the association in a Chinese population between these SNPs and VSD using a double approach: case-control and TDT designs. Among the three SNPs, only -634C allele was less frequently present in 222 patients compared to 352 controls (odds ratio: 0.76, 95% CI: 0.59-0.97, X(2)=5.06, P=0.024, not significant after a Bonferroni correction). This was significantly less transmitted to VSD patients (trios: 142) (odds ratio: 0.39, 95% CI: 0.25-0.62, X(2)=8.11, df=1, P=0.004, corrected P=0.024). A similar result was observed for haplotype -2578C/-1154G/-634C allele in both studies (in TDT: X(2)=7.51, df=1, P=0.006, corrected P=0.048). All these associations for the first time demonstrated that -634C allele was in a significant protective association against VSD, suggesting that VEGF dysregulation was involved in the pathological processes of VSD.

Research paper thumbnail of Cystic fibrosis transmembrane conductance regulator (CFTR) gene 5T allele may protect against prostate cancer: A case-control study in Chinese Han population

Journal of Cystic Fibrosis, 2008

Cystic fibrosis (CF) is caused by defects in the CF transmembrane conductance regulator (CFTR) th... more Cystic fibrosis (CF) is caused by defects in the CF transmembrane conductance regulator (CFTR) that functions as a chloride channel in epithelial cells. The most common cause of CF is the abnormal trafficking of CFTR mutants. Therefore, understanding the cellular ...

Research paper thumbnail of A novel competitive fluorescent multiplex STR polymorphism assay for rapid, reliable and single-tube screening of 22q11.2 copy-number aberrations

Electrophoresis, 2009

Copy-number aberrations of the 22q11.2 region can lead to varied resulting and complex phenotypes... more Copy-number aberrations of the 22q11.2 region can lead to varied resulting and complex phenotypes. Routine screening for these common constitutional chromosomal abnormalities requires powerful tools. A competitive fluorescent multiplex STR polymorphism assay (CFMSA) was built for detecting these aberrations. With the introduction of an internal reference and distinguishable STR polymorphism markers, this competitive fluorescent multiplex STR polymorphism assay provides complementary information about polymorphism and gene dosage in one tube simultaneously, thereby enhancing the assay sensitivity. It was first tested in 110 normal controls, and was proven to have highly polymorphic and reliable gene dosage information. Then, 476 subjects with congenital heart defect were screened according to the testing strategy of the American Heart Association, and 17 deletions and 1 duplication of 22q11.2 were correctly identified. It is expected that this assay will serve as a cost-effective alternative to existing assays for routine, large-scale screening in all at-risk individuals with either deletion or duplication in 22q11.2.

Research paper thumbnail of Promoter polymorphism of matrilin-1 gene predisposes to adolescent idiopathic scoliosis in a Chinese population

European Journal of Human Genetics, 2009

Adolescent idiopathic scoliosis (AIS) is widely recognized as a complex disorder with a strong ge... more Adolescent idiopathic scoliosis (AIS) is widely recognized as a complex disorder with a strong genetic predisposition. In previous studies, a number of extracellular matrixes (ECMs) related genes have been duplicated as candidate genes for AIS. Matrilin-1 plays an important role in the organization of the ECM, and matrilin-1 gene (MATN1) mutant mice showed similar phenotypes to scoliosis. We hypothesized that MATN1 was a candidate predisposition gene for AIS. A gene-based association study was conducted using seven tagging SNPs identified from the HapMap data. For initial screening, the seven tagSNPs were genotyped in 197 cases and 172 controls. Next, we validated any significant association in an additional sample of 222 cases and 288 controls. In addition, another 290 controls were genotyped to confirm the results. We found that allele G of rs1149048 was a significant predisposition allele of AIS (P ¼ 0.0007, odds ratio (OR) ¼ 1.35 within 95% confidence interval (CI) ¼ 1.14 -1.61), and individuals with genotype GG had a higher risk for AIS compared with AA þ AG (P ¼ 0.0001, OR ¼ 1.61 within 95% CI ¼ 1.25-2.08). Polymorphism of rs1149048 was also associated with curve severity in AIS patients. Also, a significantly higher maximum Cobb angle was found in patients with GG genotype (P ¼ 0.002). We concluded that the tagSNP rs1149048 polymorphism in the MATN1 promoter region was associated with both susceptibility and disease progression in AIS.

Research paper thumbnail of Replication of the association of the aspartic acid repeat polymorphism in the asporin gene with knee-osteoarthritis susceptibility in Han Chinese

Journal of Human Genetics, 2006

A genetic association of osteoarthritis (OA) and functional polymorphisms in the aspartic acid (D... more A genetic association of osteoarthritis (OA) and functional polymorphisms in the aspartic acid (D) repeat of the asporin gene was reported in Japanese and European Caucasians; however, the results were controversial. Our objective was to evaluate whether the D repeat polymorphism was associated with knee OA in Han Chinese. The D repeat polymorphism was genotyped in 218 patients who suffered from primary symptomatic knee OA with radiographic confirmation and in 454 age-matched controls, and the allelic association of the repeat was examined. Frequencies of the D13 and D14 alleles were similar to those of Japanese, but different from those of European Caucasians. The D14 allele was significantly over-represented in knee OA patients (P=0.0013; odds ratio 2.04; 95% confidence interval 1.32–3.15). D14 was more frequent in early-onset patients than in late-onset patients (P=0.043) and the age at onset in patients with D14 was earlier (P=0.028; log-rank test). Thus, the association of the D14 allele with knee OA susceptibility was replicated in Han Chinese. This was the first instance that association of the OA susceptibility gene was definitely replicated between different ethnic groups.

Research paper thumbnail of VEGF C−634G polymorphism is associated with protection from isolated ventricular septal defect: case–control and TDT studies

European Journal of Human Genetics, 2007

The ventricular septal defect (VSD) is the most common congenital heart defect and no candidate s... more The ventricular septal defect (VSD) is the most common congenital heart defect and no candidate susceptibility gene has been identified. Endocardial cushion and outflow septal morphogenesis, malalignment of which induces VSD, have been suggested to be mediated by the vascular endothelial growth factor (VEGF). Three single-nucleotide polymorphism (SNP) variants in promoter and 5'-UTR region of the VEGF gene, C-2578A (rs699947), G-1154A (rs1570360) and G-634C (rs2010963), were reported to alter its expression. We assessed the association in a Chinese population between these SNPs and VSD using a double approach: case-control and TDT designs. Among the three SNPs, only -634C allele was less frequently present in 222 patients compared to 352 controls (odds ratio: 0.76, 95% CI: 0.59-0.97, X(2)=5.06, P=0.024, not significant after a Bonferroni correction). This was significantly less transmitted to VSD patients (trios: 142) (odds ratio: 0.39, 95% CI: 0.25-0.62, X(2)=8.11, df=1, P=0.004, corrected P=0.024). A similar result was observed for haplotype -2578C/-1154G/-634C allele in both studies (in TDT: X(2)=7.51, df=1, P=0.006, corrected P=0.048). All these associations for the first time demonstrated that -634C allele was in a significant protective association against VSD, suggesting that VEGF dysregulation was involved in the pathological processes of VSD.

Research paper thumbnail of Cystic fibrosis transmembrane conductance regulator (CFTR) gene 5T allele may protect against prostate cancer: A case-control study in Chinese Han population

Journal of Cystic Fibrosis, 2008

Cystic fibrosis (CF) is caused by defects in the CF transmembrane conductance regulator (CFTR) th... more Cystic fibrosis (CF) is caused by defects in the CF transmembrane conductance regulator (CFTR) that functions as a chloride channel in epithelial cells. The most common cause of CF is the abnormal trafficking of CFTR mutants. Therefore, understanding the cellular ...

Research paper thumbnail of A novel competitive fluorescent multiplex STR polymorphism assay for rapid, reliable and single-tube screening of 22q11.2 copy-number aberrations

Electrophoresis, 2009

Copy-number aberrations of the 22q11.2 region can lead to varied resulting and complex phenotypes... more Copy-number aberrations of the 22q11.2 region can lead to varied resulting and complex phenotypes. Routine screening for these common constitutional chromosomal abnormalities requires powerful tools. A competitive fluorescent multiplex STR polymorphism assay (CFMSA) was built for detecting these aberrations. With the introduction of an internal reference and distinguishable STR polymorphism markers, this competitive fluorescent multiplex STR polymorphism assay provides complementary information about polymorphism and gene dosage in one tube simultaneously, thereby enhancing the assay sensitivity. It was first tested in 110 normal controls, and was proven to have highly polymorphic and reliable gene dosage information. Then, 476 subjects with congenital heart defect were screened according to the testing strategy of the American Heart Association, and 17 deletions and 1 duplication of 22q11.2 were correctly identified. It is expected that this assay will serve as a cost-effective alternative to existing assays for routine, large-scale screening in all at-risk individuals with either deletion or duplication in 22q11.2.

Research paper thumbnail of Promoter polymorphism of matrilin-1 gene predisposes to adolescent idiopathic scoliosis in a Chinese population

European Journal of Human Genetics, 2009

Adolescent idiopathic scoliosis (AIS) is widely recognized as a complex disorder with a strong ge... more Adolescent idiopathic scoliosis (AIS) is widely recognized as a complex disorder with a strong genetic predisposition. In previous studies, a number of extracellular matrixes (ECMs) related genes have been duplicated as candidate genes for AIS. Matrilin-1 plays an important role in the organization of the ECM, and matrilin-1 gene (MATN1) mutant mice showed similar phenotypes to scoliosis. We hypothesized that MATN1 was a candidate predisposition gene for AIS. A gene-based association study was conducted using seven tagging SNPs identified from the HapMap data. For initial screening, the seven tagSNPs were genotyped in 197 cases and 172 controls. Next, we validated any significant association in an additional sample of 222 cases and 288 controls. In addition, another 290 controls were genotyped to confirm the results. We found that allele G of rs1149048 was a significant predisposition allele of AIS (P ¼ 0.0007, odds ratio (OR) ¼ 1.35 within 95% confidence interval (CI) ¼ 1.14 -1.61), and individuals with genotype GG had a higher risk for AIS compared with AA þ AG (P ¼ 0.0001, OR ¼ 1.61 within 95% CI ¼ 1.25-2.08). Polymorphism of rs1149048 was also associated with curve severity in AIS patients. Also, a significantly higher maximum Cobb angle was found in patients with GG genotype (P ¼ 0.002). We concluded that the tagSNP rs1149048 polymorphism in the MATN1 promoter region was associated with both susceptibility and disease progression in AIS.

Research paper thumbnail of Replication of the association of the aspartic acid repeat polymorphism in the asporin gene with knee-osteoarthritis susceptibility in Han Chinese

Journal of Human Genetics, 2006

A genetic association of osteoarthritis (OA) and functional polymorphisms in the aspartic acid (D... more A genetic association of osteoarthritis (OA) and functional polymorphisms in the aspartic acid (D) repeat of the asporin gene was reported in Japanese and European Caucasians; however, the results were controversial. Our objective was to evaluate whether the D repeat polymorphism was associated with knee OA in Han Chinese. The D repeat polymorphism was genotyped in 218 patients who suffered from primary symptomatic knee OA with radiographic confirmation and in 454 age-matched controls, and the allelic association of the repeat was examined. Frequencies of the D13 and D14 alleles were similar to those of Japanese, but different from those of European Caucasians. The D14 allele was significantly over-represented in knee OA patients (P=0.0013; odds ratio 2.04; 95% confidence interval 1.32–3.15). D14 was more frequent in early-onset patients than in late-onset patients (P=0.043) and the age at onset in patients with D14 was earlier (P=0.028; log-rank test). Thus, the association of the D14 allele with knee OA susceptibility was replicated in Han Chinese. This was the first instance that association of the OA susceptibility gene was definitely replicated between different ethnic groups.

Research paper thumbnail of VEGF C−634G polymorphism is associated with protection from isolated ventricular septal defect: case–control and TDT studies

European Journal of Human Genetics, 2007

The ventricular septal defect (VSD) is the most common congenital heart defect and no candidate s... more The ventricular septal defect (VSD) is the most common congenital heart defect and no candidate susceptibility gene has been identified. Endocardial cushion and outflow septal morphogenesis, malalignment of which induces VSD, have been suggested to be mediated by the vascular endothelial growth factor (VEGF). Three single-nucleotide polymorphism (SNP) variants in promoter and 5'-UTR region of the VEGF gene, C-2578A (rs699947), G-1154A (rs1570360) and G-634C (rs2010963), were reported to alter its expression. We assessed the association in a Chinese population between these SNPs and VSD using a double approach: case-control and TDT designs. Among the three SNPs, only -634C allele was less frequently present in 222 patients compared to 352 controls (odds ratio: 0.76, 95% CI: 0.59-0.97, X(2)=5.06, P=0.024, not significant after a Bonferroni correction). This was significantly less transmitted to VSD patients (trios: 142) (odds ratio: 0.39, 95% CI: 0.25-0.62, X(2)=8.11, df=1, P=0.004, corrected P=0.024). A similar result was observed for haplotype -2578C/-1154G/-634C allele in both studies (in TDT: X(2)=7.51, df=1, P=0.006, corrected P=0.048). All these associations for the first time demonstrated that -634C allele was in a significant protective association against VSD, suggesting that VEGF dysregulation was involved in the pathological processes of VSD.

Research paper thumbnail of Cystic fibrosis transmembrane conductance regulator (CFTR) gene 5T allele may protect against prostate cancer: A case-control study in Chinese Han population

Journal of Cystic Fibrosis, 2008

Cystic fibrosis (CF) is caused by defects in the CF transmembrane conductance regulator (CFTR) th... more Cystic fibrosis (CF) is caused by defects in the CF transmembrane conductance regulator (CFTR) that functions as a chloride channel in epithelial cells. The most common cause of CF is the abnormal trafficking of CFTR mutants. Therefore, understanding the cellular ...

Research paper thumbnail of A novel competitive fluorescent multiplex STR polymorphism assay for rapid, reliable and single-tube screening of 22q11.2 copy-number aberrations

Electrophoresis, 2009

Copy-number aberrations of the 22q11.2 region can lead to varied resulting and complex phenotypes... more Copy-number aberrations of the 22q11.2 region can lead to varied resulting and complex phenotypes. Routine screening for these common constitutional chromosomal abnormalities requires powerful tools. A competitive fluorescent multiplex STR polymorphism assay (CFMSA) was built for detecting these aberrations. With the introduction of an internal reference and distinguishable STR polymorphism markers, this competitive fluorescent multiplex STR polymorphism assay provides complementary information about polymorphism and gene dosage in one tube simultaneously, thereby enhancing the assay sensitivity. It was first tested in 110 normal controls, and was proven to have highly polymorphic and reliable gene dosage information. Then, 476 subjects with congenital heart defect were screened according to the testing strategy of the American Heart Association, and 17 deletions and 1 duplication of 22q11.2 were correctly identified. It is expected that this assay will serve as a cost-effective alternative to existing assays for routine, large-scale screening in all at-risk individuals with either deletion or duplication in 22q11.2.