| Project/Area Number |
16H05272
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Legal medicine
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| Research Institution | University of Fukui |
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Principal Investigator |
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| Research Collaborator |
IIDA Reiko
UEKI Misuzu
KOMINATO Yoshihiko
TAKESHITA Haruo
KOBAYASHI Motohiro
KAWAI Yasuyuki
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥16,380,000 (Direct Cost: ¥12,600,000、Indirect Cost: ¥3,780,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2017: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2016: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
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| Keywords | DNase / 遺伝的多型 / 一塩基多型 / 心筋梗塞 / 自己免疫疾患 / 遺伝的リスクファクター / 遺伝的多様性 / DNase I / SNP / Indel / 酵素 / がん / DNase 1L2 / 非同義置換型 SNP / cell-free DNA / 診断マーカー / DNase family |
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| Outline of Final Research Achievements |
We could demonstrate that; (1) Total 42 genetic variants producing a loss-of-function could be identified in DNASE1. (2) In DNase 1-like 3 and DNase II genes, which have assumed to be involved in rheumatoid arthritis, 4 and 5 non-synonymous SNPs abolishing the activity, respectively, were found. Furthermore, the synonymous SNPs in the latter exhibited a significant association with rheumatoid arthritis in the Japanese populations. (3) DNase I-like 2 has been assumed to play a role in the etiology of parakeratosis through incomplete degradation of DNA in the epidermis. In DNASE1L2, 32 missense SNPs and 19 SNPs originating from frameshift/ nonsense variants resulted in loss of function of the enzyme. (4) Almost all the variants producing a loss-of-function exhibited extremely low genetic heterogeneity. (5) Each of the minor alleles for these genetic variants may serve as one of genetic risk factors for various diseases, even though they lack a worldwide genetic distribution.
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| Academic Significance and Societal Importance of the Research Achievements |
自己免疫疾患や心筋梗塞などに関与するDNase I遺伝子では42個の、関節リウマチに関与するDNase 1-like 3およびDNase II遺伝子ではそれぞれ4及び5個の、尋常性乾癬における不全角化病変異に係るDNase 1-like 2遺伝子では51個の不活性な酵素を産生するgenetic variantsを同定した。これらはin vivo DNase活性を減弱させるものであり、それら疾患のリスクファクターとなる。本研究の結果はDNase familyが自己免疫疾患などの遺伝的背景の一部となることの確証をもたらすものであり、もって、オーダーメード医療の推進に寄与できる。
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