Apoptodic gene analysis in idiopathic talipes equinovarus (clubfoot)
Apoptodic gene analysis in idiopathic talipes equinovarus (clubfoot)
复制标题
DOI：
10.1097/blo.0b013e318073c2d9
复制
发表时间：
2007-09-01
影响因子：
4.2
通讯作者：
Hecht, Jacqueline T.
中科院分区：
文献类型：
--
作者：
Ester, Audrey R.;Yerman, Gayle;Hecht, Jacqueline T.
特发性马蹄内翻足，也被称为马蹄内翻足，是一种常见的出生缺陷，发生在1000名活产儿中的一名。这是一种复杂的疾病，多基因和环境因素可能在病因中起作用。包括2q31-33在内的几个染色体缺失区与马蹄内翻足相关，可能含有与特发性马蹄内翻足表型有关的基因。此前，2q31-33中的两个短串联重复序列GATA149B10和132SI371与特发性马蹄内翻足相关。对特发性马蹄内翻足家系中GATA149B10附近的3个凋亡基因Casp8、Casp10和CFLAR的单核苷酸多态性(SNPs)进行了基因分型。Casp10基因中的rs3731714与特发性马蹄内翻足存在连锁关系，提示在特发性马蹄内翻足的发生发展中起重要作用的凋亡基因通路存在变异。我们对210个单纯性三联体和139个多重家系中的7个凋亡基因Casp3、Casp8、CASP9、Casp10、Bid、Bid、Bcl2和Apaf1的SNPs进行了基因分型，并检测了它们与特发性马蹄内翻足的连锁和关联。每个基因中的一个SNP提供了与特发性马蹄内翻足有关的提示证据。从这些SNPs构建的几种单倍型显示了改变的传递。这些数据表明，凋亡基因的遗传变异可能在特发性马蹄内翻足的发生中起作用。
Idiopathic talipes equinovarus, also known as clubfoot, is a common birth defect occurring in one of 1000 live births. It is a complex disorder in which multiple genes and environmental factors may play an etiologic role. Several chromosomal deletion regions, including 2q31-33, are associated with talipes equinovarus and may harbor genes that contribute to the idiopathic talipes equinovarus phenotype. Previously, two STRs in the 2q31-33, GATA149B10 and 132SI371, showed linkage with association to idiopathic talipes equinovarus. Single nucleotide polymorphisms (SNPs) in three apoptotic genes (Casp8, Casp10, and CFLAR) near GATA149B10 were genotyped in idiopathic talipes equinovarus families. rs3731714 in Casp10 showed linkage with association, suggesting variation in the apoptotic gene pathway, which is important in limb morphogenesis, and may play a role in the development of idiopathic talipes equinovarus. We genotyped SNPs spanning seven apoptotic genes-Casp3, Casp8, Casp9, Casp10, Bid, Bcl-2 and Apafl-in 210 simplex trios and 139 multiplex families and tested for linkage and association to idiopathic talipes equinovarus. One SNP in each of the genes provided suggestive evidence of association with idiopathic talipes equinovarus. Several haplotypes constructed from these SNPs displayed altered transmission. These data suggest genetic variation in apoptotic genes may play a role in development of idiopathic talipes equinovarus.