Analysis of responsible region in chromosome 21 for the disease phenotype in Down syndrome

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461546
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Osaka University
• Principal Investigator: KITABATAKE YASUJI 大阪大学, 医学(系)研究科(研究院), 助教 (80506494)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: iPS細胞 / ゲノム編集 / ダウン症候群 / 小児科

Outline of Final Research Achievements

Down syndrome (DS) is caused by the presence of three copies of human chromosome 21. Among various medical symptoms, DS patients have an increased likelihood of certain hematopoietic abnormalities. We focused on transient abnormal myelopoiesis (TAM) in DS, which are characteristically associated with somatic mutations in GATA1. To better understand pathological mechanism and identify the causal genes in TAM, we constructed cellular disease models using human induced pluripotent stem cells (iPSCs) and genome-editing technologies. By generating a partial trisomy 21 iPSCs in which a 4-Mb region was deleted from a single copy of chromosome 21, we succeeded in proving this segment as a critical region for TAM.

Free Research Field

幹細胞研究、小児科学