A group of Professor Keiichi Ohzono and Assistant Professor Koji Kitabatake of Osaka University Graduate School elucidated the mechanism of blood cell proliferation abnormality (TAM) that frequently occurs in newborns with Down syndrome by combining genome editing technology and chromosomal engineering with human iPS cells. bottom.It identified a region where genes that cause hematopoietic abnormalities gather and clarified the main gene clusters in it, and was published in the American scientific journal "Cell Reports".

 Down's syndrome, which occurs at a high rate among pediatric genetic diseases of 700 in 1, is caused by an increase in the number of chromosome 21 to 3 (trisomy).Since hundreds of genes cause quantitative changes at the same time, the number of combinations of gene changes that need to be grasped in order to elucidate the pathological condition is enormous, and analysis is extremely difficult.In addition, Down's syndrome has various complications, of which TAM, which is found in more than 10% of newborns, is said to involve mutations in the GATA21 gene on the X chromosome in addition to abnormalities on the 1st chromosome. It was unclear how they interact to cause abnormalities and which genes are involved.

 While it was considered difficult to create an experimental model for Down's syndrome, in this study, iPS cells were created from "umbilical cord blood" that has the same gene structure as newborns, and the GATA1 gene was edited in various ways to form chromosomes and genotypes. We succeeded in reproducing the pathophysiology of TAM by producing multiple iPS cells with different combinations.As a result of examining them, it was found that the genes responsible for TAM are concentrated in a specific region on chromosome 21.It was found that the expression of mutant GATA1 is promoted by the action of this region, and the pathological condition of TAM appears by the action of trisomy of chromosome 21.

 The results of this study not only clarified the pathogenic mechanism of TAM in Down's syndrome, but also provided an opportunity to understand the pathogenic mechanism leading to leukemia.It is expected that the development of diagnosis and treatment methods for complications of Down's syndrome will be greatly promoted in the future.

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