Investigation for new glaucoma gene using the next-generation sequencer

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09927
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56060:Ophthalmology-related
• Research Institution: Tohoku University
• Principal Investigator: FUSE NOBUO 東北大学, 東北メディカル・メガバンク機構, 教授 (10302134)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 緑内障 / 次世代シークエンサー / 全エクソン解析 / 原因遺伝子探索 / ゲノムワイド関連解析

Outline of Final Research Achievements

(1) Whole exome analysis was performed for adult-onset glaucoma of 20 families or more. Candidate genes were extracted by amino acid substitution and mode of inheritance. A V161M mutation in the OPTN gene, which is also the causative gene for amyotrophic lateral sclerosis, was found in one family. (2) Whole exome analysis was performed on 31 people from 29 families with congenital glaucoma. CYP1B1 gene abnormality (including 4 new mutations) was observed in 10 patients in 9 families and 3 new FOXC1 gene mutations in 4 patients in 3 families. 30% showed abnormalities in the CYP1B1 gene and 10% showed abnormalities in the FOXC1 gene. (3) Genome-wide association study of genes related to axial length, which is a risk of developing glaucoma, was performed. 31 loci were identified and basic data for glaucoma analysis were constructed.

Free Research Field

眼科

Academic Significance and Societal Importance of the Research Achievements

緑内障に関しては、種々の発症機序による層別化がいまだ行われておらず、緑内障として一連の疾患群とされている状態である。緑内障は、低頻度の多型と高頻度の多型が原因となる不均一な疾患であると考えられるが、国内外ともに網羅的な解析は進んでいないのが現状である。緑内障の発症に効果が大きい低頻度の多型解析を、全エクソン解析により進めること、また緑内障の発症のリスクである因子を検索することにより、高頻度の多型だけでは説明できな遺伝力の欠損問題が解明できると期待される。今後の個別化医療に、日本人における緑内障の原因遺伝子の同定、抽出と、緑内障発症のリスク因子との関連解析は大きく寄与すると考えられる。