Global analysis of A-to-I RNA editing reveals association with common disease variants

被引：20

作者：

Franzen, Oscar ^{[1
]}

Ermel, Raili ^{[2
]}

Sukhavasi, Katyayani ^{[3
]}

Jain, Rajeev ^{[3
]}

Jain, Anamika ^{[3
]}

Betsholtz, Christer ^{[1
,4
]}

Giannarelli, Chiara ^{[5
,6
]}

Kovacic, Jason C. ^{[5
]}

Ruusalepp, Arno ^{[2
,3
,7
]}

Skogsberg, Josefin ^{[8
]}

Hao, Ke ^{[6
]}

Schadt, Eric E. ^{[6
,7
]}

Bjorkegren, Johan L. M. ^{[1
,3
,6
,7
]}

机构：

[1] Karolinska Inst, Integrated Cardio Metab Ctr, Huddinge, Sweden

[2] Tartu Univ Hosp, Dept Cardiac Surg, Tartu, Estonia

[3] Univ Tartu, Inst Biomed & Translat Med, Dept Pathophysiol, Tartu, Estonia

[4] Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden

[5] Icahn Sch Med Mt Sinai, Cardiovasc Res Ctr, New York, NY 10029 USA

[6] Icahn Sch Med Mt Sinai, Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY 10029 USA

[7] Clin Gene Networks AB, Stockholm, Sweden

[8] Karolinska Inst, Dept Med Biochem & Biophys, Solna, Sweden

来源：

PEERJ | 2018年 / 6卷

基金：

美国国家卫生研究院;

关键词：

RNA editing; Gene expression; Quantitative trait loci; RNA-seq; Bioinformatics; Biostatistics; GENOME-WIDE ASSOCIATION; CORONARY-ARTERY-DISEASE; ACCURATE IDENTIFICATION; LOCI; RISK; GENE; ALU; DATABASE; SITES; ATHEROSCLEROSIS;

D O I：

10.7717/peerj.4466

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

RNA editing modifies transcripts and may alter their regulation or function. In humans, the most common modification is adenosine to inosine (A-to-I). We examined the global characteristics of RNA editing in 4,301 human tissue samples. More than 1.6 million A-to-I edits were identified in 62% of all protein-coding transcripts. mRNA recoding was extremely rare; only 11 novel recoding sites were uncovered. Thirty single nucleotide polymorphisms from genome-wide association studies were associated with RNA editing; one that influences type 2 diabetes (rs2028299) was associated with editing in ARPIN. Twenty-five genes, including LRP11 and PLIN5, had editing sites that were associated with plasma lipid levels. Our findings provide new insights into the genetic regulation of RNA editing and establish a rich catalogue for further exploration of this process.

引用

页数：27

共 79 条

[1] A map of human genome variation from population-scale sequencing [J].

Altshuler, David ;

Durbin, Richard M. ;

Abecasis, Goncalo R. ;

Bentley, David R. ;

Chakravarti, Aravinda ;

Clark, Andrew G. ;

Collins, Francis S. ;

De la Vega, Francisco M. ;

Donnelly, Peter ;

Egholm, Michael ;

Flicek, Paul ;

Gabriel, Stacey B. ;

Gibbs, Richard A. ;

Knoppers, Bartha M. ;

Lander, Eric S. ;

Lehrach, Hans ;

Mardis, Elaine R. ;

McVean, Gil A. ;

Nickerson, DebbieA. ;

Peltonen, Leena ;

Schafer, Alan J. ;

Sherry, Stephen T. ;

Wang, Jun ;

Wilson, Richard K. ;

Gibbs, Richard A. ;

Deiros, David ;

Metzker, Mike ;

Muzny, Donna ;

Reid, Jeff ;

Wheeler, David ;

Wang, Jun ;

Li, Jingxiang ;

Jian, Min ;

Li, Guoqing ;

Li, Ruiqiang ;

Liang, Huiqing ;

Tian, Geng ;

Wang, Bo ;

Wang, Jian ;

Wang, Wei ;

Yang, Huanming ;

Zhang, Xiuqing ;

Zheng, Huisong ;

Lander, Eric S. ;

Altshuler, David L. ;

Ambrogio, Lauren ;

Bloom, Toby ;

Cibulskis, Kristian ;

Fennell, Tim J. ;

Gabriel, Stacey B. .

NATURE, 2010, 467 (7319) :1061-1073

[2] HTSeq-a Python']Python framework to work with high-throughput sequencing data [J].

Anders, Simon ;

Pyl, Paul Theodor ;

Huber, Wolfgang .

BIOINFORMATICS, 2015, 31 (02) :166-169

[3] The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease [J].

Astle, William J. ;

Elding, Heather ;

Jiang, Tao ;

Allen, Dave ;

Ruklisa, Dace ;

Mann, Alice L. ;

Mead, Daniel ;

Bouman, Heleen ;

Riveros-Mckay, Fernando ;

Kostadima, Myrto A. ;

Lambourne, John J. ;

Sivapalaratnam, Suthesh ;

Downes, Kate ;

Kundu, Kousik ;

Bomba, Lorenzo ;

Berentsen, Kim ;

Bradley, John R. ;

Daugherty, Louise C. ;

Delaneau, Olivier ;

Freson, Kathleen ;

Garner, Stephen F. ;

Grassi, Luigi ;

Guerrero, Jose ;

Haimel, Matthias ;

Janssen-Megens, Eva M. ;

Kaan, Anita ;

Kamat, Mihir ;

Kim, Bowon ;

Mandoli, Amit ;

Marchini, Jonathan ;

Martens, Joost H. A. ;

Meacham, Stuart ;

Megy, Karyn ;

O'Connell, Jared ;

Petersen, Romina ;

Sharifi, Nilofar ;

Sheard, Simon M. ;

Staley, James R. ;

Tuna, Salih ;

van der Ent, Martijn ;

Walter, Klaudia ;

Wang, Shuang-Yin ;

Wheeler, Eleanor ;

Wilder, Steven P. ;

Iotchkova, Valentina ;

Moore, Carmel ;

Sambrook, Jennifer ;

Stunnenberg, Hendrik G. ;

Di Angelantonio, Emanuele ;

Kaptoge, Stephen .

CELL, 2016, 167 (05) :1415-+

[4] Widespread A-to-I RNA editing of alu-containing mRNAs in the human transcriptome [J].

Athanasiadis, A ;

Rich, A ;

Maas, S .

PLOS BIOLOGY, 2004, 2 (12) :2144-2158

[5] GenABEL: an R library for genome-wide association analysis [J].

Aulchenko, Yurii S. ;

Ripke, Stephan ;

Isaacs, Aaron ;

Van Duijn, Cornelia M. .

BIOINFORMATICS, 2007, 23 (10) :1294-1296

[6] Accurate identification of A-to-I RNA editing in human by transcriptome sequencing [J].

Bahn, Jae Hoon ;

Lee, Jae-Hyung ;

Li, Gang ;

Greer, Christopher ;

Peng, Guangdun ;

Xiao, Xinshu .

GENOME RESEARCH, 2012, 22 (01) :142-150

[7] RNA editing by adenosine deaminases that act on RNA [J].

Bass, BL .

ANNUAL REVIEW OF BIOCHEMISTRY, 2002, 71 :817-846

[8] A-to-I RNA editing occurs at over a hundred million genomic sites, located in a majority of human genes [J].

Bazak, Lily ;

Haviv, Ami ;

Barak, Michal ;

Jacob-Hirsch, Jasmine ;

Deng, Patricia ;

Zhang, Rui ;

Isaacs, Farren J. ;

Rechavi, Gideon ;

Li, Jin Billy ;

Eisenberg, Eli ;

Levanon, Erez Y. .

GENOME RESEARCH, 2014, 24 (03) :365-376

[9] MAJOR TRANSCRIPT OF THE FRAMESHIFTED COXLL GENE FROM TRYPANOSOME MITOCHONDRIA CONTAINS 4 NUCLEOTIDES THAT ARE NOT ENCODED IN THE DNA [J].

BENNE, R ;

VANDENBURG, J ;

BRAKENHOFF, JPJ ;

SLOOF, P ;

VANBOOM, JH ;

TROMP, MC .

CELL, 1986, 46 (06) :819-826

[10] Active Alu retrotransposons in the human genome [J].

Bennett, E. Andrew ;

Keller, Heiko ;

Mills, Ryan E. ;

Schmidt, Steffen ;

Moran, John V. ;

Weichenrieder, Oliver ;

Devine, Scott E. .

GENOME RESEARCH, 2008, 18 (12) :1875-1883

← 1 2 3 4 5 6 7 8 →