Exon sequencing of PAX3 and T (brachyury) in cases with spina bifida.
Exon sequencing of PAX3 and T (brachyury) in cases with spina bifida.
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DOI：
10.1002/bdra.23163
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发表时间：
2013-09
期刊：
影响因子：
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通讯作者：
Mitchell LE
中科院分区：
文献类型：
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作者：
Agopian AJ;Bhalla AD;Boerwinkle E;Finnell RH;Grove ML;Hixson JE;Shimmin LC;Sewda A;Stuart C;Zhong Y;Zhu H;Mitchell LE
基于动物和人类的研究，PAX 3和T（短尾畸形）是脊柱裂的候选基因。然而，这两种基因都没有被确定为这种情况的危险因素。桑格测序法用于鉴定114例脊柱裂患者所有PAX 3和T外显子及启动子区的变异。对于已知的变异，病例中的等位基因频率与公共数据库中的等位基因频率进行了比较，使用未经调整的比值比。在父母中对新变体进行基因分型，并评估预测的功能影响。我们确定了PAX 3（n=2）和T（n=3）中的常见变异，其病例中的等位基因频率与至少一个公共数据库中报告的等位基因频率显著不同。我们还在脊柱裂病例中鉴定了PAX 3（n=11）和T（n=1）的新变体。几种新的PAX 3变体被预测为高度保守和/或影响基因功能或表达。这些研究提供了一些证据，表明PAX 3和T的常见变异与脊柱裂有关。在受影响的个体中也发现了这些基因的罕见和新变异。然而，需要更多的研究来确定这些变异是否会影响脊柱裂的风险。
Based on studies in animals and humans, PAX3 and T (brachyury) are candidate genes for spina bifida. However, neither gene has been definitively identified as a risk factor for this condition. Sanger sequencing was used to identify variants in all PAX3 and T exons and promoter regions in 114 spina bifida cases. For known variants, allele frequencies in cases were compared to those from public databases using unadjusted odds ratios. Novel variants were genotyped in parents and assessed for predicted functional impact. We identified common variants in PAX3 (n=2) and T (n=3) for which the allele frequencies in cases were significantly different from those reported in at least one public database. We also identified novel variants in both PAX3 (n=11) and T (n=1) in spina bifida cases. Several of the novel PAX3 variants are predicted to be highly conserved and/or impact gene function or expression. These studies provide some evidence that common variants of PAX3 and T are associated with spina bifida. Rare and novel variants in these genes were also identified in affected individuals. However, additional studies will be required to determine whether these variants influence the risk of spina bifida.