Genetic predisposition to biliary atresia by comprehensive genomic analyses on monozygotic twins with unilateral onset

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K07844
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Osaka University
• Principal Investigator: Bessho Kazuhiko 大阪大学, 医学系研究科, 准教授 (80423169)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 胆道閉鎖症 / 一卵性双生児 / エクソーム解析

Outline of Final Research Achievements

To determine the genetic predisposition in the etiology of biliary atresia, DNA was extracted from blood cells of four pairs of monozygotic twins who developed biliary atresia unilaterally and subjected to exome analysis.
Single nucleotide polymorphisms that were discordant between the twins were examined, but no polymorphisms or polymorphic genes common to all four twin pairs were identified. Next, copy number variant analysis was performed on the twins, and no common genes with different copy numbers were found between the twin pairs. Furthermore, we compared affected and unaffected twins at loci previously reported as susceptibility polymorphisms for biliary atresia, but no single nucleotide polymorphisms that differed between the twins were identified.

Free Research Field

小児肝臓病学

Academic Significance and Societal Importance of the Research Achievements

胆道閉鎖症は世界中で最多の小児肝移植適応疾患であり、本邦でも全肝移植の中で最多適応疾患である。一方で慢性的なドナー不足、高額な医療費などは解決すべき重要な課題となっている。これまで胆道閉鎖症には有効な内科的治療法は存在しないが、根本的治療の開発には病因・発症機序の解明が必須である。本研究目的は、胆道閉鎖症の遺伝的素因を、本来同一の遺伝子を有するはずの一卵性双生児のうち片側のみ胆道閉鎖症を発症したペアのゲノム配列を比較することにより明らかにすることを目的としたが、研究期間中に感受性遺伝子は同定されなかった。更なる解析の追加、胆道閉鎖症の発症における環境因子の探索が必要である。