Research for the causative genes of the congenital abnormality using analysis of the action points of teratogenic factors

据认为，超过一半的先天缺陷是由遗传因素和环境因素相互作用引起的。在本报告中，我们分析了环境因素作用机制的新方法。在过去的两年中，我们用基因捕捉法筛选了培养细胞中过表达基因的靶基因，并分析了它们在体内的表达模式；2)我们筛选了包括脊椎动物畸形在内的遗传性疾病的致病基因。1)我们以ES细胞和软骨细胞的前体ATDC5细胞为筛选对象，筛选了Pax1/9的靶基因，并检测到了Pumilio和siena两个候选靶基因。分析这些基因在正常小鼠胚胎和突变小鼠胚胎中的表达模式，以检测转录的调控。2)对两例Jarcho-Levin综合征患者的致病基因Dll-3进行了分析，该基因正在进行中。对疑似Schwarz-Jampel综合征的患者进行了Pumilio基因分析，发现该基因定位于该病的临界区，但已证实该病是由2000年Perlecan基因突变引起的。

It is believed that more than half of the congenital defects is caused with the interaction between genetic factors and circumstance factors. In this report, we analyzed the new method how to approach the action mechanism of the circumstance factors.In last two years, 1) we screened the target genes of the overexpressed gene in the cultured cells with gene trap method and analyzed their in vivo expression pattern, 2) we screened the causative genes of the inherited diseases including vertebrate deformity.1) We used ES cells and ATDC5 cell line, progenitor of chondrocyte, for the screening of target genes of Pax1/9. We detected two genes, Pumilio and Siena, as candidate target gene. These genes are analyzed expression pattern in both of normal and mutant mouse embryos, in order to detect the regulation of transcription.2) Two patients diagnosed as Jarcho-Levin syndrome are analyzed in its causative gene, Dll-3, which is in progress. The patient suspected as Schwarz-Jampel syndrome is analyzed in Pumilio gene, which is found to be mapped to critical region of this disease, however, it is proved that this disease is caused with the mutation of Perlecan in 2000.