SMIM1 underlies the Vel blood group and influences red blood cell traits

被引：82

作者：

Cvejic, Ana ^{[1
,2
]}

Haer-Wigman, Lonneke ^{[3
,4
]}

Stephens, Jonathan C. ^{[1
,5
,6
]}

Kostadima, Myrto ^{[7
]}

Smethurst, Peter A. ^{[1
,5
,6
]}

Frontini, Mattia ^{[1
,5
,6
]}

van den Akker, Emile ^{[4
,8
]}

Bertone, Paul ^{[7
]}

Bielczyk-Maczynska, Ewa ^{[1
,2
,5
,6
]}

Farrow, Samantha ^{[1
,5
,6
]}

Fehrmann, Rudolf S. N. ^{[9
]}

Gray, Alan ^{[10
]}

de Haas, Masja ^{[3
,4
]}

Haver, Vincent G. ^{[11
]}

Jordan, Gregory

Karjalainen, Juha ^{[9
]}

Kerstens, Hindrik H. D. ^{[12
]}

Kiddle, Graham ^{[1
,5
,6
]}

Lloyd-Jones, Heather ^{[1
,5
,6
]}

Needs, Malcolm ^{[10
]}

Poole, Joyce ^{[13
]}

Soussan, Aicha Ait ^{[3
,4
]}

Rendon, Augusto ^{[1
,5
,6
,14
]}

Rieneck, Klaus ^{[15
]}

Sambrook, Jennifer G. ^{[1
,5
,6
]}

Schepers, Hein ^{[16
,17
]}

Sillje, Herman H. W. ^{[11
]}

Sipos, Botond ^{[7
]}

Swinkels, Dorine ^{[18
]}

Tamuri, Asif U. ^{[7
]}

Verweij, Niek ^{[11
]}

Watkins, Nicholas A. ^{[6
]}

Westra, Harm-Jan ^{[9
]}

Stemple, Derek ^{[2
]}

Franke, Lude ^{[9
]}

Soranzo, Nicole ^{[2
]}

Stunnenberg, Hendrik G. ^{[12
]}

Goldman, Nick ^{[7
]}

van der Harst, Pim ^{[9
,11
]}

van der Schoot, C. Ellen ^{[3
,4
]}

Ouwehand, Willem H. ^{[1
,2
,5
,6
]}

Albers, Cornelis A. ^{[1
,2
,5
,6
,19
]}

机构：

[1] Univ Cambridge, Dept Haematol, Cambridge, England

[2] Wellcome Trust Sanger Inst, Cambridge, England

[3] Sanquin Res, Dept Expt Immunohaematol, Amsterdam, Netherlands

[4] Univ Amsterdam, Acad Med Ctr, Landsteiner Lab, NL-1105 AZ Amsterdam, Netherlands

[5] Cambridge Biomed Res Ctr, NIHR, Cambridge, England

[6] Natl Hlth Serv NHS Blood & Transplant, Cambridge, England

[7] European Bioinformat Inst, EMBL, Cambridge, England

[8] Sanquin Res, Dept Hematopoiesis, Amsterdam, Netherlands

[9] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands

[10] NHS Blood & Transplant, London, England

[11] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands

[12] Radboud Univ Nijmegen, Dept Mol Biol, Fac Sci, Nijmegen Ctr Mol Life Sci, NL-6525 ED Nijmegen, Netherlands

[13] NHS Blood & Transplant, Int Blood Grp Reference Lab, Bristol, Avon, England

[14] Inst Publ Hlth, MRC, Biostat Unit, Cambridge, England

[15] Copenhagen Univ Hosp, Rigshosp, Dept Clin Immunol, Copenhagen, Denmark

[16] Univ Groningen, Univ Med Ctr Groningen, Dept Expt Hematol, Groningen, Netherlands

[17] Univ Groningen, Univ Med Ctr Groningen, Dept Stem Cell Biol, Groningen, Netherlands

[18] Radboud Univ Nijmegen, Med Ctr, Dept Lab Med, Lab Genet Endocrine & Metab Dis, NL-6525 ED Nijmegen, Netherlands

[19] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands

来源：

NATURE GENETICS | 2013年 / 45卷 / 05期

基金：

英国惠康基金;

关键词：

GENE-EXPRESSION; ALIGNMENT; VARIANTS;

D O I：

10.1038/ng.2603

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

The blood group Vel was discovered 60 years ago(1), but the underlying gene is unknown. Individuals negative for the Vel antigen are rare and are required for the safe transfusion of patients with antibodies to Vel(2). To identify the responsible gene, we sequenced the exomes of five individuals negative for the Vel antigen and found that four were homozygous and one was heterozygous for a low-frequency 17-nucleotide frameshift deletion in the gene encoding the 78-amino-acid transmembrane protein SMIM1. A follow-up study showing that 59 of 64 Vel-negative individuals were homozygous for the same deletion and expression of the Vel antigen on SMIM1-transfected cells confirm SMIM1 as the gene underlying the Vel blood group. An expression quantitative trait locus (eQTL), the common SNP rs1175550 contributes to variable expression of the Vel antigen (P = 0.003) and influences the mean hemoglobin concentration of red blood cells (RBCs; P = 8.6 x 10(-15))(3). In vivo, zebrafish with smim1 knockdown showed a mild reduction in the number of RBCs, identifying SMIM1 as a new regulator of RBC formation. Our findings are of immediate relevance, as the homozygous presence of the deletion allows the unequivocal identification of Vel-negative blood donors.

引用

页码：542 / U115

页数：6

共 27 条

[1]

BLUEPRINT to decode the epigenetic signature written in blood [J].

Adams, David ;

Altucci, Lucia ;

Antonarakis, Stylianos E. ;

Ballesteros, Juan ;

Beck, Stephan ;

Bird, Adrian ;

Bock, Christoph ;

Boehm, Bernhard ;

Campo, Elias ;

Caricasole, Andrea ;

Dahl, Fredrik ;

Dermitzakis, Emmanouil T. ;

Enver, Tariq ;

Esteller, Manel ;

Estivill, Xavier ;

Ferguson-Smith, Anne ;

Fitzgibbon, Jude ;

Flicek, Paul ;

Giehl, Claudia ;

Graf, Thomas ;

Grosveld, Frank ;

Guigo, Roderic ;

Gut, Ivo ;

Helin, Kristian ;

Jarvius, Jonas ;

Kueppers, Ralf ;

Lehrach, Hans ;

Lengauer, Thomas ;

Lernmark, Ake ;

Leslie, David ;

Loeffler, Markus ;

Macintyre, Elizabeth ;

Mai, Antonello ;

Martens, Joost H. A. ;

Minucci, Saverio ;

Ouwehand, Willem H. ;

Pelicci, Pier Giuseppe ;

Pendeville, Helene ;

Porse, Bo ;

Rakyan, Vardhman ;

Reik, Wolf ;

Schrappe, Martin ;

Schuebeler, Dirk ;

Seifert, Martin ;

Siebert, Reiner ;

Simmons, David ;

Soranzo, Nicole ;

Spicuglia, Salvatore ;

Stratton, Michael ;

Stunnenberg, Hendrik G. .

NATURE BIOTECHNOLOGY, 2012, 30 (03) :224-226

[2]

Singular value decomposition for genome-wide expression data processing and modeling [J].

Alter, O ;

Brown, PO ;

Botstein, D .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (18) :10101-10106

[3]

An integrated map of genetic variation from 1,092 human genomes [J].

Altshuler, David M. ;

Durbin, Richard M. ;

Abecasis, Goncalo R. ;

Bentley, David R. ;

Chakravarti, Aravinda ;

Clark, Andrew G. ;

Donnelly, Peter ;

Eichler, Evan E. ;

Flicek, Paul ;

Gabriel, Stacey B. ;

Gibbs, Richard A. ;

Green, Eric D. ;

Hurles, Matthew E. ;

Knoppers, Bartha M. ;

Korbel, Jan O. ;

Lander, Eric S. ;

Lee, Charles ;

Lehrach, Hans ;

Mardis, Elaine R. ;

Marth, Gabor T. ;

McVean, Gil A. ;

Nickerson, Deborah A. ;

Schmidt, Jeanette P. ;

Sherry, Stephen T. ;

Wang, Jun ;

Wilson, Richard K. ;

Gibbs, Richard A. ;

Dinh, Huyen ;

Kovar, Christie ;

Lee, Sandra ;

Lewis, Lora ;

Muzny, Donna ;

Reid, Jeff ;

Wang, Min ;

Wang, Jun ;

Fang, Xiaodong ;

Guo, Xiaosen ;

Jian, Min ;

Jiang, Hui ;

Jin, Xin ;

Li, Guoqing ;

Li, Jingxiang ;

Li, Yingrui ;

Li, Zhuo ;

Liu, Xiao ;

Lu, Yao ;

Ma, Xuedi ;

Su, Zhe ;

Tai, Shuaishuai ;

Tang, Meifang .

NATURE, 2012, 491 (7422) :56-65

[4]

Daniels G.L., 2002, HUMAN BLOOD GROUPS

[5]

Use of the zebrafish system to study primitive and definitive hematopoiesis [J].

de Jong, JLO ;

Zon, LI .

ANNUAL REVIEW OF GENETICS, 2005, 39 :481-501

[6]

A framework for variation discovery and genotyping using next-generation DNA sequencing data [J].

DePristo, Mark A. ;

Banks, Eric ;

Poplin, Ryan ;

Garimella, Kiran V. ;

Maguire, Jared R. ;

Hartl, Christopher ;

Philippakis, Anthony A. ;

del Angel, Guillermo ;

Rivas, Manuel A. ;

Hanna, Matt ;

McKenna, Aaron ;

Fennell, Tim J. ;

Kernytsky, Andrew M. ;

Sivachenko, Andrey Y. ;

Cibulskis, Kristian ;

Gabriel, Stacey B. ;

Altshuler, David ;

Daly, Mark J. .

NATURE GENETICS, 2011, 43 (05) :491-+

[7]

INTRAEMBRYONIC HEMATOPOIETIC-CELL MIGRATION DURING VERTEBRATE DEVELOPMENT [J].

DETRICH, HW ;

KIERAN, MW ;

CHAN, FY ;

BARONE, LM ;

YEE, K ;

RUNDSTADLER, JA ;

PRATT, S ;

RANSOM, D ;

ZON, LI .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (23) :10713-10717

[8]

An integrated encyclopedia of DNA elements in the human genome [J].

Dunham, Ian ;

Kundaje, Anshul ;

Aldred, Shelley F. ;

Collins, Patrick J. ;

Davis, CarrieA. ;

Doyle, Francis ;

Epstein, Charles B. ;

Frietze, Seth ;

Harrow, Jennifer ;

Kaul, Rajinder ;

Khatun, Jainab ;

Lajoie, Bryan R. ;

Landt, Stephen G. ;

Lee, Bum-Kyu ;

Pauli, Florencia ;

Rosenbloom, Kate R. ;

Sabo, Peter ;

Safi, Alexias ;

Sanyal, Amartya ;

Shoresh, Noam ;

Simon, Jeremy M. ;

Song, Lingyun ;

Trinklein, Nathan D. ;

Altshuler, Robert C. ;

Birney, Ewan ;

Brown, James B. ;

Cheng, Chao ;

Djebali, Sarah ;

Dong, Xianjun ;

Dunham, Ian ;

Ernst, Jason ;

Furey, Terrence S. ;

Gerstein, Mark ;

Giardine, Belinda ;

Greven, Melissa ;

Hardison, Ross C. ;

Harris, Robert S. ;

Herrero, Javier ;

Hoffman, Michael M. ;

Iyer, Sowmya ;

Kellis, Manolis ;

Khatun, Jainab ;

Kheradpour, Pouya ;

Kundaje, Anshul ;

Lassmann, Timo ;

Li, Qunhua ;

Lin, Xinying ;

Marinov, Georgi K. ;

Merkel, Angelika ;

Mortazavi, Ali .

NATURE, 2012, 489 (7414) :57-74

[9]

Trans-eQTLs Reveal That Independent Genetic Variants Associated with a Complex Phenotype Converge on Intermediate Genes, with a Major Role for the HLA [J].

Fehrmann, Rudolf S. N. ;

Jansen, Ritsert C. ;

Veldink, Jan H. ;

Westra, Harm-Jan ;

Arends, Danny ;

Bonder, Marc Jan ;

Fu, Jingyuan ;

Deelen, Patrick ;

Groen, Harry J. M. ;

Smolonska, Asia ;

Weersma, Rinse K. ;

Hofstra, Robert M. W. ;

Buurman, Wim A. ;

Rensen, Sander ;

Wolfs, Marcel G. M. ;

Platteel, Mathieu ;

Zhernakova, Alexandra ;

Elbers, Clara C. ;

Festen, Eleanora M. ;

Trynka, Gosia ;

Hofker, Marten H. ;

Saris, Christiaan G. J. ;

Ophoff, Roel A. ;

van den Berg, Leonard H. ;

van Heel, David A. ;

Wijmenga, Cisca ;

Meerman, Gerard J. Te ;

Franke, Lude .

PLOS GENETICS, 2011, 7 (08)

[10]

Ensembl 2012 [J].

Flicek, Paul ;

Amode, M. Ridwan ;

Barrell, Daniel ;

Beal, Kathryn ;

Brent, Simon ;

Carvalho-Silva, Denise ;

Clapham, Peter ;

Coates, Guy ;

Fairley, Susan ;

Fitzgerald, Stephen ;

Gil, Laurent ;

Gordon, Leo ;

Hendrix, Maurice ;

Hourlier, Thibaut ;

Johnson, Nathan ;

Kaehaeri, Andreas K. ;

Keefe, Damian ;

Keenan, Stephen ;

Kinsella, Rhoda ;

Komorowska, Monika ;

Koscielny, Gautier ;

Kulesha, Eugene ;

Larsson, Pontus ;

Longden, Ian ;

McLaren, William ;

Muffato, Matthieu ;

Overduin, Bert ;

Pignatelli, Miguel ;

Pritchard, Bethan ;

Riat, Harpreet Singh ;

Ritchie, Graham R. S. ;

Ruffier, Magali ;

Schuster, Michael ;

Sobral, Daniel ;

Tang, Y. Amy ;

Taylor, Kieron ;

Trevanion, Stephen ;

Vandrovcova, Jana ;

White, Simon ;

Wilson, Mark ;

Wilder, Steven P. ;

Aken, Bronwen L. ;

Birney, Ewan ;

Cunningham, Fiona ;

Dunham, Ian ;

Durbin, Richard ;

Fernandez-Suarez, Xose M. ;

Harrow, Jennifer ;

Herrero, Javier ;

Hubbard, Tim J. P. .

NUCLEIC ACIDS RESEARCH, 2012, 40 (D1) :D84-D90

← 1 2 3 →