Cell-specific protein phenotypes for the autoimmune locus IL2RA using a genotype-selectable human bioresource

被引：218

作者：

Dendrou, Calliope A. ^{[1
]}

Plagnol, Vincent ^{[1
]}

Fung, Erik ^{[1
]}

Yang, Jennie H. M. ^{[1
]}

Downes, Kate ^{[1
]}

Cooper, Jason D. ^{[1
]}

Nutland, Sarah ^{[1
]}

Coleman, Gillian ^{[1
]}

Himsworth, Matthew ^{[1
]}

Hardy, Matthew ^{[1
]}

Burren, Oliver ^{[1
]}

Healy, Barry ^{[1
]}

Walker, Neil M. ^{[1
]}

Koch, Kerstin ^{[2
]}

Ouwehand, Willem H. ^{[2
,3
]}

Bradley, John R. ^{[4
,5
]}

Wareham, Nicholas J. ^{[6
]}

Todd, John A. ^{[1
]}

Wicker, Linda S. ^{[1
]}

机构：

[1] Univ Cambridge, Addenbrookes Hosp, Juvenile Diabet Res Fdn,Cambridge Inst Med Res, Wellcome Trust Diabet & Inflammat Lab, Cambridge CB2 2QQ, England

[2] Univ Cambridge & NHS Blood & Transplant Cambridge, Dept Haematol, Cambridge, England

[3] Wellcome Trust Sanger Inst, Dept Human Genet, Cambridge, England

[4] Univ Cambridge, Addenbrookes Hosp, Div Resp Med, Dept Med,Sch Clin Med, Cambridge CB2 2QQ, England

[5] Univ Cambridge, Dept Med, Div Resp Med, Papworth Hosp,Sch Clin Med, Cambridge CB2 2QQ, England

[6] Addenbrookes Hosp, Med Res Council Epidemiol Unit, Inst Metab Sci, Cambridge, England

来源：

NATURE GENETICS | 2009年 / 41卷 / 09期

基金：

英国医学研究理事会; 英国惠康基金; 美国国家卫生研究院;

关键词：

REGULATORY T-CELLS; NOD MICE; DIABETES-MELLITUS; ALLELIC VARIANTS; HUMAN IMMUNOLOGY; RNA-SEQ; INTERLEUKIN-2; IL-2; RECEPTOR; DISEASE;

D O I：

10.1038/ng.434

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Genome-wide association studies (GWAS) have identified over 300 regions associated with more than 70 common diseases(1). However, identifying causal genes within an associated region remains a major challenge(1,2). One approach to resolving causal genes is through the dissection of gene-phenotype correlations. Here we use polychromatic flow cytometry to show that differences in surface expression of the human interleukin-2 (IL-2) receptor alpha (IL2RA, or CD25) protein are restricted to particular immune cell types and correlate with several haplotypes in the IL2RA region that have previously been associated with two autoimmune diseases, type 1 diabetes (T1D) and multiple sclerosis(2-4). We confirm our strongest gene-phenotype correlation at the RNA level by allele-specific expression (ASE). We also define key parameters for the design and implementation of post-GWAS gene-phenotype investigations and demonstrate the usefulness of a large bioresource of genotype-selectable normal donors from whom fresh, primary cells can be analyzed.

引用

页码：1011 / U80

页数：7

共 30 条

[1] Functional analysis of highly defined, FACS-isolated populations of human regulatory CD4+CD25+ T cells [J].