Pathological and physiological involvement of DNase with certain diseases

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H03065
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 58040:Forensics medicine-related
• Research Institution: Shimane University
• Principal Investigator: TAKESHITA HARUO 島根大学, 学術研究院医学・看護学系, 教授 (90292599)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 核酸分解酵素 / DNase / 遺伝的多型 / 疾患素因 / 病態遺伝

Outline of Final Research Achievements

Considering the positions in the DNase I protein corresponding to the various nonsense SNPs, all of the other nonsense SNPs and frameshift variants registered in the Ensembl database (https://asia.ensembl.org) appear likely to exert a pathogenetic effect through loss of the activity. Accordingly, a total of 60 genetic variants in the DNase 1 gene (DNASE1) inducing abolishment or marked reduction of the DNase I activity could be identified as genetic risk factors for autoimmunity, irrespective of how sparsely they were distributed in the population. It was noteworthy that SNP p.Gln244Arg, reportedly associated with autoimmunity and reducing the activity to about half of that of the wild type, and SNP p.Arg107Gly, abolishing the activity completely, were distributed worldwide and in African populations at the polymorphic level, respectively.

Free Research Field

法医学

Academic Significance and Societal Importance of the Research Achievements

これまでDNA多型(SNPs等)の違いに基づく、疾患素因や中毒代謝に関わる様々な遺伝的多型に関する研究を推進してきた。昨今の犯罪の悪質・巧妙化に伴って、法医学鑑識科学分野において、被疑者や被害者などを特定する上で個人識別精度の向上が益々要請されている。近年の分子生物学領域の進歩に立脚したＤＮＡ多型の発見・法医学実務への導入によって個人識別精度の飛躍的向上がもたらされている。本研究により上記観点において、学術的意義や社会的意義を向上させた。