Association of the GLI gene with ventricular septal defect after the susceptibility gene being narrowed to 3.56 cM in 12q13.
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 (chi(2) = 5.918, P = 0.015), G11388A (chi(2) = 8.067, P = 0.005), and G11625T (chi(2) = 11.842, P = 0.001). Haplotype analysis showed a strong linkage disequilibrium between G11888C and G11388A (D' = 0.999), but in significant (chi(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.
Department of Medical Genetics, China Medical University, Shenyang 110001, China. qgr1973@yahoo.com.cn
Guang-rong
GR
Qiu
Li-guo
LG
Gong
Guang
G
He
Xiao-yan
XY
Xu
Na
N
Xin
Gui-feng
GF
Sun
Yi-hua
YH
Yuan
Kai-lai
KL
Sun
D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006345:Heart Septal Defects, Ventricular / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D018895:Microsatellite Repeats; D014157:Transcription Factors / Q000235:genetics*; D000071676:Zinc Finger Protein GLI1
C400551:GLI1 protein, human; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1