A testis-specific gene, TPTE, encodes a putative transmembrane tyrosine phosphatase and maps to the pericentromeric region of human chromosomes 21 and 13, and to chromosomes 15, 22, and Y

To contribute to the creation of a transcription map of human chromosome 21 (HC21) and to the identification of genes that may be involved in the path ogenesis of Down syndrome, exon trapping was performed from HC21-specific c osmids covering the entire chromosome. More than 700 exons have been identi fied to date. One such exon, hmc01a06, maps to YAC 831B6 which contains mar ker D21Z1 (alphoid repeats) and had previously been localized to the perice ntromeric region of HC21. Northern-blot analysis revealed a 2.5-kb mRNA spe cies strongly and exclusively expressed in the testis. We cloned the corres ponding full-length cDNA, which encodes a predicted polypeptide of 551 amin o acids with at least two potential transmembrane domains and a tyrosine ph osphatase motif. The cDNA has sequence homology to chicken tensin, bovine a uxilin and rat cyclin-G associated kinase (GAK). The entire polypeptide seq uence also has significant homology to tumor suppressor PTEN/MMAC1 protein. We termed this novel gene/protein TPTE (transmembrane phosphatase with ten sin homology). Polymerase chain reaction amplification, fluorescent in situ hybridization, Southern-blot and sequence analysis using monochromosomal s omatic cell hybrids showed that this gene has highly homologous copies on H C13, 15, 22, and Y, in addition to its HC21 copy or copies. The estimated m inimum number of copies of the TPTE gene in the haploid human genome is 7 i n male and 6 in female. Zoo-blot analysis showed that TPTE is conserved bet ween humans and other species. The biological function of the TPTE gene is presently unknown; however, its expression pattern, sequence homologies, an d the presence of a potential tyrosine phosphatase domain suggest that it m ay be involved in signal transduction pathways of the endocrine or spermato genetic function of the testis. It is also unknown whether all copies of TP TE are functional or whether some are pseudogenes. TPTE is, to our knowledg e, the gene located closest to the human centromeric sequences.