CHARACTERIZATION AND MAPPING TO HUMAN-CHROMOSOME 8Q24.3 OF LY-6-RELATED GENE-9804 ENCODING AN APPARENT HOMOLOG OF MOUSE TSA-1

The 9804 gene, which encodes a human Ly-6 protein most similar to mous e differentiation Ag TSA-1/Sca-2, has also been called RIG-E. Like mou se TSA-1, it has a broad tissue distribution with varied expression le vels in normal human tissues and tumor cell lines. Like some members o f the murine Ly-6 family, the 9804 gene is responsive to IFNs, particu larly IFN-alpha. Overlapping genomic fragments spanning the 9804 gene (5543 bp) have been isolated and characterized. The gene organization is analogous to that of known mouse Ly-6 genes. The first exon, 2296 b p upstream from exon II, is entirely untranslated. The three coding ex ons (II, III, and IV) are separated by short introns of 321 and 131 bp , respectively. Primers were developed for specific amplification of 9 804 gene fragments. Screening of human-hamster somatic cell hybrids an d yeast artificial chromosomes (YACs) indicated that the gene is dista l to c-Myc, located in the q arm of human chromosome 8. No positives w ere detected from the Centre d'Etude du Polymorphisme Humain mega-YAC A or B panels, nor from bacterial artificial chromosome libraries; two positive cosmids (c101F1 and c157F6) were isolated from a human chrom osome 8 cosmid library (LA08NC01). Fluorescence in situ hybridization of metaphase spreads of chromosome 8, containing hybrid cell line 706- B6 clone 17 (CL-17) with cosmid c101F1, placed the 9804 gene close to the telomere at 8q24.3. This mapping is significant, since the region shares a homology with a portion of mouse chromosome 15, which extends into band E where Ly-6 genes reside. Moreover, the gene encoding E48, the homologue of mouse Ly-6 molecule ThB, has also been mapped to 8q2 4.