講演情報
[BO-4]マルチオミクス解析から明らかにしたAlu配列の介在した遺伝子異常
○木下 善仁1,2,4, 新田 和広2, 八塚 由紀子2, 岡崎 敦子2, 杉浦 歩2, 伏見 拓矢3, 大道 納菜子4, 大竹 明5,6, 村山 圭3,7, 岡崎 康司2,8 (1.近畿大学 理工学部 生命科学科, 2.順天堂大学大学院 難治性疾患診断・治療学講座/難病の診断と治療研究センター, 3.千葉県こども病院 代謝科, 4.近畿大学大学院 総合理工学研究科 理学専攻 遺伝カウンセラー養成課程, 5.埼玉医科大学 小児科学・ゲノム医療学, 6.埼玉医科大学 難病センター, 7.千葉県こども病院 遺伝診療センター, 8.国立研究開発法人 理化学研究所 生命医科学研究センター 応用ゲノム解析技術研究チーム)
[Objective] Mitochondrial disease is the most common inborn errors of metabolism that present with abnormal mitochondrial function. This disease can be caused by both mitochondrial and nuclear-encoded genes. Although conventional panel sequencing and whole exome sequencing are effective for diagnosis, a certain number of cases remain unresolved in practice. Therefore, it is necessary to investigate the cause of the disease from a multifaceted approach. In this study, we aimed to elucidate the cause of undiagnosed cases by combining whole genome sequencing, RNA sequencing and proteome analysis. [Methods] We searched for causative variants by whole genome sequencing, RNA sequencing, and proteome analysis, focusing on cases that had not been diagnosed by panel sequencing or whole exome sequencing. In cases that we found candidate causative variants, we performed PCR and Sanger sequencing of family members to elucidate the genetic form. [Results and discussion] We found candidate causative genes with abnormal gene expression by multi-omics analysis. The whole genome sequencing identified deletions of several kilobases in causative genes, including NDUFV2, NFU1, and others. Detailed examination of the deletion sites revealed that the deletions were mediated by Alu element, suggesting that recombination between different Alu element caused the deletions, and that the deletions were accompanied by Alu mediated insertion. It is expected that such Alu-mediated structural variations will be found as the number of analyses by whole genome sequencing increases.