ISOLATION AND CHARACTERIZATION OF XE169, A NOVEL HUMAN GENE THAT ESCAPES X-INACTIVATION

Overlapping cDNA clones for a novel human X-linked gene, XE169, have b een isolated and characterized. The composite cDNA sequence comprises 5910 bp (or 5901 bp) plus a poly(A) tail, with a 531 bp 5' and 696 bp 3' untranslated regions. The sequence represents a full-length or near full-length cDNA for the gene since Northern blot analysis reveals on ly a single prominent band similar to 6 kb in size. Alternative splici ng generates two distinct transcripts either containing or missing a s tretch of nine nucleotides in the XE169 single large open reading fram e, which in turn predict two XE169 protein isoforms composed of 1557 a nd 1560 amino acids, respectively. Southern hybridization analysis of a panel of human-mouse somatic cell hybrids containing various portion s of translocated human X chromosomes has assigned XE169 to the proxim al half of the X short arm between Xp21.1 and the centromere. XE169 is expressed in multiple human tissues tested and homologous sequences e xist on the human Y chromosome and in the genomes of five other euther ian mammals examined. RT-PCR analysis of somatic cell hybrids containi ng either an active or an inactive human X chromosome on a rodent back ground demonstrated that XE169 escapes X-inactivation.