File | |
language |
eng
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Author |
Fujihara , Junko
Department of Legal Medicine, Shimane University School of Medicine
Ueki, Misuzu
Division of Medical Genetics and Biochemistry, University of Fukui
Kimura-Kataoka, Kaori
Department of Legal Medicine, Shimane University School of Medicine
Iida, Reiko
Division of Life Sciences, Faculty of Medical Sciences, University of Fukui
Takeshita, Haruo
Department of Legal Medicine, Shimane University School of Medicine
Yasuda, Toshihiro
Division of Medical Genetics and Biochemistry, University of Fukui
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Description | OBJECTIVE: To continue our previous investigations, we have extensively investigated the function of the 61, 41, and 35 non-synonymous single nucleotide polymorphisms (SNPs) in the human genes encoding DNASE1, DNASE1L3, and DNASE2, respectively, potentially relevant to autoimmune diseases.
METHODS: The site-directed mutagenesis was employed to amino acid-substituted constructs corresponding to each SNP. The COS-7 cells were transfected with each vector and DNase activity was assayed by the single radial enzyme diffusion method. By using PolyPhen-2, changes in the DNase function of each non-synonymous SNP were predicted. Genotyping of all the non-synonymous SNPs was performed in 14 different populations including 3 ethnic groups using the polymerase chain reaction followed by the restriction fragment length polymorphism method. RESULTS: Expression analysis demonstrated these SNPs to be classified into four categories with regard to the effect on DNase activity: SNPs not affecting the activity level, ones reducing it, ones abolishing it, and ones elevating it. In particular, 9, 5, and 4 SNPs producing a loss-of-function variant of the enzymes in DNASE1, DNASE1L3, and DNASE2, respectively, were confirmed. SNPs producing DNase loss of function can be estimated by PolyPhen-2 to be "probably damaging" with a high accuracy of prediction. Almost all of these functional SNPs producing a loss of function or substantially low activity-harboring forms exhibited a mono-allelic distribution in all of the populations. CONCLUSION: A minor allele of functional SNPs, despite the remarkably low genetic heterogeneity of the SNPs, might be a genetic risk factor for autoimmune diseases. |
Subject | Autoimmunity
deoxyribonuclease (DNase) family
functional SNPs
genetic distribution
genotype
loss-of-function
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Journal Title |
Immunological investigations
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Volume | 45
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Issue | 5
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Start Page | 406
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End Page | 419
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ISSN | 08820139
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Published Date | 2016-07
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DOI | |
DOI Date | 2017-09-06
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PubMed ID | |
NCID | AA10519794
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Publisher | Taylor & Francis
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NII Type |
Journal Article
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Format |
PDF
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Rights | This is an Accepted Manuscript of an article published by Taylor & Francis in Immunological investigations on 2016, available online: http://www.tandfonline.com/10.3109/08820139.2016.1157813.
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Text Version |
著者版
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Gyoseki ID | e32475
e31895
e31830
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OAI-PMH Set |
Faculty of Medicine
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