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- Title
The humanTlocus and spina bifida risk.
- Authors
Jensen, Liselotte E.; Barbaux, Sandrine; Hoess, Katy; Fraterman, Sven; Whitehead, Alexander S.; Mitchell, Laura E.
- Abstract
The transcription factor T is essential for mesoderm formation and axial development during embryogenesis. Embryonic genotype for a single-nucleotide polymorphism in intron 7 ofT(TIVS7T/C) has been associated with the risk of spina bifida in some but not all studies. We developed a novel genotyping assay for theTIVS7polymorphism using heteroduplex generator methology. This assay was used to genotype spina bifida case-parent trios and the resulting data were analyzed using the transmission disequilibrium test and log-linear analyses. Analyses of these data demonstrated that heterozygous parents transmit theTIVS7-C allele to their offspring with spina bifida significantly more frequently than expected under the assumption of Mendelian inheritance (63 vs 50%,P=0.02). Moreover, these analyses suggest that theTIVS7-C allele acts in a dominant fashion, such that individuals carrying one or more copies of this allele have a 1.6-fold increased risk of spina bifida compared with individuals with zero copies.In silicoanalysis of the sequence surrounding this polymorphism revealed a potential target site for olfactory neuron-specific factor-1, a transcription factor expressed in the neural tube during development, spanning the polymorphic site. Several other putative, developmentally important and/or environmentally responsive transcription factor-binding sites were also identified close to theTIVS7polymorphism. TheTIVS7polymorphism or a variant that is in linkage disequilibrium with theTIVS7polymorphism may, therefore, play a role inTgene expression and influence the risk of spina bifida.
- Subjects
SPINA bifida; TRANSCRIPTION factors; MESODERM; EMBRYOLOGY; GENETIC polymorphisms; GENE expression; FAMILIAL diseases
- Publication
Human Genetics, 2004, Vol 115, Issue 6, p475
- ISSN
0340-6717
- Publication type
Article
- DOI
10.1007/s00439-004-1185-8