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Publication : Assembly and annotation of human chromosome 2q33 sequence containing the CD28, CTLA4, and ICOS gene cluster: analysis by computational, comparative, and microarray approaches.

First Author  Ling V Year  2001
Journal  Genomics Volume  78
Issue  3 Pages  155-68
PubMed ID  11735222 Mgi Jnum  J:73271
Mgi Id  MGI:2154829 Doi  10.1006/geno.2001.6655
Citation  Ling V, et al. (2001) Assembly and annotation of human chromosome 2q33 sequence containing the CD28, CTLA4, and ICOS gene cluster: analysis by computational, comparative, and microarray approaches. Genomics 78(3):155-68
abstractText  Human chromosome 2q33 is an immunologically important region based on the linkage of numerous autoimmune diseases to the CTLA4 locus. Here, we sequenced and assembled 2q33 bacterial artificial chromosome (BAC) clones, resulting in 381,403 bp of contiguous sequence containing genes encoding a NADH: ubiquinone oxidoreductase, the costimulatory receptors CD28, CTLA4, and ICOS, and a HERV-H type endogenous retrovirus located 366 bp downstream of ICOS in the reverse orientation. Genomic microarray expression analysis using differentially activated T-cell RNA against a subcloned CTLA4/ICOS BAC library revealed upregulation of CTLA4 and ICOS sequences, plus antisense ICOS transcripts generated by the HERV-H, suggesting a potential mechanism for ICOS regulation. We identified four nonlinked, polymorphic, simple repetitive sequence elements in this region, which may be used to delineate genetic effects of ICOS and CTLA4 in disease populations. Comparative genomic analysis of mouse genomic Icos sequences revealed 60% sequence identity in the 5' UTR and regions between exon 2 and the 3' UTR, suggesting the importance of ICOS gene function.
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