ファイル | |
言語 |
英語
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著者 |
藤原 純子
島根大学医学部法医学講座
植木 美鈴
福井大学医学部病態遺伝生化学領域
木村 かおり
島根大学医学部法医学講座
飯田 礼子
福井大学医学部・生命基礎科学領域
竹下 治男
島根大学医学部法医学講座
安田 年博
福井大学医学部病態遺伝生化学領域
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内容記述(抄録等) | 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. |
主題 | Autoimmunity
deoxyribonuclease (DNase) family
functional SNPs
genetic distribution
genotype
loss-of-function
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掲載誌名 |
Immunological investigations
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巻 | 45
|
号 | 5
|
開始ページ | 406
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終了ページ | 419
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ISSN | 08820139
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発行日 | 2016-07
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DOI | |
DOI公開日 | 2017-09-06
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PubMed ID | |
NCID | AA10519794
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出版者 | Taylor & Francis
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資料タイプ |
学術雑誌論文
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ファイル形式 |
PDF
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権利関係 | 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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著者版/出版社版 |
著者版
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業績ID | e32475
e31895
e31830
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部局 |
医学部
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