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

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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.