CHARACTERIZATION OF THE CODING SEQUENCE AND FINE MAPPING OF THE HUMANDFFRY GENE AND COMPARATIVE EXPRESSION ANALYSIS AND MANNING TO THE SXR(B) INTERVAL OF THE MOUSE Y-CHROMOSOME OF THE DFFRY GENE

DFFRY (the Y-linked homologue of the DFFRX Drosophila fat-facets relat ed X gene) maps to proximal Yq11.2 within the interval defining the AZ Fa spermatogenic phenotype, The complete coding region of DFFRY has be en sequenced and shows 89% identity to the X-linked gene elf the nucle otide level, In common with DFFRX,the potential amino acid sequence co ntains the conserved Cys and His domains characteristic of ubiquitin C -terminal hydrolases. The human DFFRY mRNA is expressed in a wide rang e of adult and embryonic tissues, including testis, whereas the homolo gous mouse Dffry gene is expressed specifically in the testis, Analysi s of three azoospermic male patients has shown that DFFRY is deleted f rom the Y chromosome in these individuals, Two patients have a testicu lar phenotype which resembles Sertoli cell-only syndrome, and the thir d diminished spermatogenesis. In all three patients, the deletions ext end from close to the 3' end into the gene, removing the entire coding sequence of DFFRY. The mouse Dffry gene maps to the Sxr(b) deletion i nterval on the short arm of the mouse Y chromosome and its expression in mouse testis can first be detected between 7.5 and 10.5 days after birth when type A and B spermatogonia and pre-leptotene and leptotene spermatocytes are present.