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The human T locus and spina bifida risk
Liselotte E Jensen1, Sandrine Barbaux, Katy Hoess
1Department of Pharmacology and Center for Pharmacogenetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Human Genetics
|September 28, 2004
Summary
A specific gene variant (TIVS7-C) in the T gene increases spina bifida risk by 1.6-fold. This genetic factor is transmitted more often from parents to affected children, suggesting a role in neural tube development.
Area of Science:
- Developmental Biology
- Genetics
- Medical Research
Background:
- The transcription factor T is crucial for embryonic development, particularly mesoderm formation and axial patterning.
- A single-nucleotide polymorphism in intron 7 of the T gene (TIVS7 T/C) has been inconsistently linked to spina bifida risk.
Purpose of the Study:
- To investigate the association between the TIVS7 polymorphism and spina bifida risk.
- To develop and utilize a novel genotyping assay for the TIVS7 polymorphism.
Main Methods:
- Development of a novel genotyping assay using heteroduplex generator methodology.
- Genotyping of spina bifida case-parent trios.
- Analysis of genetic data using transmission disequilibrium and log-linear analyses.
- In silico analysis of the TIVS7 polymorphism region for transcription factor-binding sites.
Main Results:
- Heterozygous parents transmitted the TIVS7-C allele to offspring with spina bifida more frequently than expected (63% vs. 50%, P=0.02).
- The TIVS7-C allele demonstrated a dominant effect, increasing spina bifida risk by 1.6-fold in individuals with one or more copies.
- In silico analysis identified potential transcription factor-binding sites near the TIVS7 polymorphism, including one for olfactory neuron-specific factor-1.
Conclusions:
- The TIVS7-C allele is significantly associated with an increased risk of spina bifida.
- This polymorphism may influence T gene expression through interactions with developmental transcription factors, thereby affecting neural tube development and spina bifida risk.