Allelic variation of the inducible costimulator (ICOS) gene: detection of polymorphisms, analysis of the promoter region, and extended haplotype estimation

被引:20
作者
Andersen, ADH
Lange, M
Lillevang, ST
机构
[1] Odense Univ Hosp, Dept Clin Immunol, DK-5000 Odense C, Denmark
[2] Tech Univ Denmark, Bioctr, DK-2800 Lyngby, Denmark
来源
TISSUE ANTIGENS | 2003年 / 61卷 / 04期
关键词
costimulation; haplotype estimation; ICOS; polymorphism; T lymphocytes; transcription;
D O I
10.1034/j.1399-0039.2003.00019.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The human chromosome region 2q33 including the three costimulatory molecules CD28, CTLA-4 and ICOS, has been subject to much attention due to its linkage to a number of autoimmune diseases. The search for the causal relationship of this linkage has revealed several polymorphisms, but no variations in the amino acid sequences except for one polymorphism in, the leader sequence of CTLA-4. In the present study, we examined the ICOS gene of an unrelated group of healthy donors from the Danish population. We were able to report 16 intronic SNP, one intronic G-insert and two repeat regions in intron 4, consistent with the [T](n) and the [GT](n) regions reported in a Japanese study. Putative haplotypes for the established SNP and repeat polymorphisms have been estimated by computational analysis. Sequencing of similar to3500 by of the upstream region of ICOS revealed an additional eight SNP of which two resided in putative NF-kB and Sp1 sites In accordance with. previous studies we detected no variations in the coding regions except for a rare polymorphism that was found in one donor in the last codon of exon 5, which lead to a heterozygous genotype, but no amino acid change. This suggests that regulation of transcription rather than protein structure could be a possible mechanism in the explanation of linkage.
引用
收藏
页码:276 / 285
页数:10
相关论文
共 22 条
  • [1] [Anonymous], 2000, ARLEQUIN SOFTWARE PO
  • [2] BROOKS AR, 1991, J BIOL CHEM, V266, P7848
  • [3] The B7 family of ligands and its receptors: New pathways for costimulation and inhibition of immune responses
    Carreno, BM
    Collins, M
    [J]. ANNUAL REVIEW OF IMMUNOLOGY, 2002, 20 : 29 - 53
  • [4] The CD28-related molecule ICOS is required for effective T cell-dependent immune responses
    Coyle, AJ
    Lehar, S
    Lloyd, C
    Tian, J
    Delaney, T
    Manning, S
    Nguyen, T
    Burwell, T
    Schneider, H
    Gonzalo, JA
    Gosselin, M
    Owen, LR
    Rudd, CE
    Gutierrez-Ramos, JC
    [J]. IMMUNITY, 2000, 13 (01) : 95 - 105
  • [5] Genetic polymorphism of the human ICOS gene
    Haimila, KE
    Partanen, JA
    Holopainen, PM
    [J]. IMMUNOGENETICS, 2002, 53 (12) : 1028 - 1032
  • [6] ICOS is an inducible T-cell co-stimulator structurally and functionally related to CD28
    Hutloff, A
    Dittrich, AM
    Beier, KC
    Eljaschewitsch, B
    Kraft, R
    Anagnostopoulos, I
    Kroczek, RA
    [J]. NATURE, 1999, 397 (6716) : 263 - 266
  • [7] Association studies of CTLA-4, CD28, and ICOS gene polymorphisms with type 1 diabetes in the Japanese population
    Ihara, K
    Ahmed, S
    Nakao, F
    Kinukawa, N
    Kuromaru, R
    Matsuura, N
    Iwata, I
    Nagafuchi, S
    Kohno, H
    Miyako, K
    Hara, T
    [J]. IMMUNOGENETICS, 2001, 53 (06) : 447 - 454
  • [8] Interleukin-13 gene expression is regulated by GATA-3 in T cells - Role of a critical association of a GATA and two GATG motifs
    Lavenu-Bombled, C
    Trainor, CD
    Makeh, I
    Romeo, PH
    Max-Audit, I
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (21) : 18313 - 18321
  • [9] Assembly and annotation of human chromosome 2q33 sequence cluster containing the CD28, CTLA4, arid ICOS gene cluster:: Analysis by computational, comparative, and microarray approaches
    Ling, V
    Wu, PW
    Finnerty, HF
    Agostino, MJ
    Graham, JR
    Chen, SJ
    Jussiff, JM
    Fisk, GJ
    Miller, CP
    Collins, M
    [J]. GENOMICS, 2001, 78 (03) : 155 - 168
  • [10] ICOS is critical for CD40-mediated antibody class switching
    McAdam, AJ
    Greenwald, RJ
    Levin, MA
    Chernova, T
    Malenkovich, N
    Ling, V
    Freeman, GJ
    Sharpe, AH
    [J]. NATURE, 2001, 409 (6816) : 102 - 105