Background Our previous research has suggested that genes around D12S1056 in 12q13 may confer susceptibility to ventricular septal defect （VSD） in humans. The present study was to define the chromosome region assign...Background Our previous research has suggested that genes around D12S1056 in 12q13 may confer susceptibility to ventricular septal defect （VSD） in humans. The present study was to define the chromosome region assignment by transmission disequilibrium test （TDT）, and to identify the important candidate gene by family-based association study and haplotype analysis. Methods Surrounding D12S1056, ten microsatellite markers including D12S329, D12S305, D12S1662, D12S1056, D12S1293, D12S334, D12S102, D12S83, D12S1655 and D12S1691 were chosen, and TDT was performed in 62 nuclear family trios each consisting of an affected child and two healty parents. Subsequently, the GLI gene, a positional candidate gene that maps to the target region, was selected for further analysis. Three single nucleotide polymorphisms （SNPs）, G11888C, G11388A, and G11625T, were selected for family-based association study and haplotype analysis. Results VSD was significantly associated with all selected markers except D12S1691 [72.2 centi morgen （cM）] and D12S1700 （75.76 cM）. VSD was also significantly associated with G11888C （X^2 = 5.918, P = 0.015）, G11388A （X^2 = 8.067, P = 0.005）, and G11625T （X^2 = 11.842, P = 0.001）. Haplotype analysis showed a strong linkage disequilibrium between G11888C and G11388A （D＇=0.999）, but in significant （X^2 = 1.035, df = 2, P 〉 0.05）. Conclusions The susceptibility gene of VSD was mapped to 3.56 cM in 12q13 by TDT, and the GLI gene, an important candidate in the target region, was associated with VSD.展开更多
TBX5, as a member of the T-box-containing transcription factor family, encodes a protein of 518 amino acids and is expressed in the embryonic heart and developing limb tissues.1 The coding region of TBX5 cDNA is 1.5 k...TBX5, as a member of the T-box-containing transcription factor family, encodes a protein of 518 amino acids and is expressed in the embryonic heart and developing limb tissues.1 The coding region of TBX5 cDNA is 1.5 kb with eight exons including the N-terminal portion, the DNA binding domain and C-terminal region. We reported that the abnormality in transcription level of the TBX5 gene might be the mechanism underlying human simple congenital heart disease in the absence of TBX5 mutations.展开更多
基金This work was supported by grants from the National Natural Science Foundation of China (No. 30200305 and No. 30070411) and Educational Department Science Funds of Liaoning Province (No. 202013133 and No. 2004C045).
文摘Background Our previous research has suggested that genes around D12S1056 in 12q13 may confer susceptibility to ventricular septal defect （VSD） in humans. The present study was to define the chromosome region assignment by transmission disequilibrium test （TDT）, and to identify the important candidate gene by family-based association study and haplotype analysis. Methods Surrounding D12S1056, ten microsatellite markers including D12S329, D12S305, D12S1662, D12S1056, D12S1293, D12S334, D12S102, D12S83, D12S1655 and D12S1691 were chosen, and TDT was performed in 62 nuclear family trios each consisting of an affected child and two healty parents. Subsequently, the GLI gene, a positional candidate gene that maps to the target region, was selected for further analysis. Three single nucleotide polymorphisms （SNPs）, G11888C, G11388A, and G11625T, were selected for family-based association study and haplotype analysis. Results VSD was significantly associated with all selected markers except D12S1691 [72.2 centi morgen （cM）] and D12S1700 （75.76 cM）. VSD was also significantly associated with G11888C （X^2 = 5.918, P = 0.015）, G11388A （X^2 = 8.067, P = 0.005）, and G11625T （X^2 = 11.842, P = 0.001）. Haplotype analysis showed a strong linkage disequilibrium between G11888C and G11388A （D＇=0.999）, but in significant （X^2 = 1.035, df = 2, P 〉 0.05）. Conclusions The susceptibility gene of VSD was mapped to 3.56 cM in 12q13 by TDT, and the GLI gene, an important candidate in the target region, was associated with VSD.
基金This work was supported by the National Natural Science Foundation of China （No.30400485）.
文摘TBX5, as a member of the T-box-containing transcription factor family, encodes a protein of 518 amino acids and is expressed in the embryonic heart and developing limb tissues.1 The coding region of TBX5 cDNA is 1.5 kb with eight exons including the N-terminal portion, the DNA binding domain and C-terminal region. We reported that the abnormality in transcription level of the TBX5 gene might be the mechanism underlying human simple congenital heart disease in the absence of TBX5 mutations.
