Characterisation of the coding sequence and fine mapping of the human DFFRY gene and comparative expression analysis and mapping to the Sxrb interval of the mouse Y chromosome of the Dffry gene

Abstract

DFFRY (the Y-linked homologue of the DFFRX Drosophila fat-facets related X gene) maps to proximal Yq11.2 within the interval defining the AZFa spermatogenic phenotype. The complete coding region of DFFRY has been sequenced and shows 89% identity to the X-linked gene at the nucleotide level. In common with DFFRX , the potential amino acid sequence contains the conserved Cys and His domains characteristic of ubiquitin C-terminal hydrolases. The human DFFRY mRNA is expressed in a wide range of adult and embryonic tissues, including testis, whereas the homologous mouse Dffry gene is expressed specifically in the testis. Analysis of three azoospermic male patients has shown that DFFRY is deleted from the Y chromosome in these individuals. Two patients have a testicular phenotype which resembles Sertoli cell-only syndrome, and the third diminished spermatogenesis. In all three patients, the deletions extend from close to the 3' end into the gene, removing the entire coding sequence of DFFRY. The mouse Dffry gene maps to the Sxrb deletion interval 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.

Possible role of USP26 in patients with severely impaired spermatogenesis

“…5,6,7 Another ubiquitin-specific protease gene involved in spermatogenesis is USP9Y. Brown et al 8 showed that Dffry, the mouse homologue of USP9Y, is expressed in the gametes. The USP9Y gene is located in the AZFa region of the Y chromosome.…”

Identification of Ubiquitin-specific Protease 9X (USP9X) as a Deubiquitinase Acting on Ubiquitin-Peroxin 5 (PEX5) Thioester Conjugate

“…USP9X is a 290-kDa DUB encoded in the X chromosome of humans, mice, and rats (58 -60). We note that some of the peptides matching USP9X might also be derived from USP9Y (see footnote in supplemental Table S2), a DUB homologous to USP9X but encoded in the Y chromosome (58,61). Although the presence of USP9Y in rat liver is presently doubtful (USP9Y, in contrast to USP9X, is not expressed in mouse liver; see Ref.…”

“…Actually, such a possibility is quite plausible because USP9X and USP9Y are almost identical proteins (61). However, considering that the complete deletion of the USP9Y-encoding gene in men has no deleterious effects (63), whereas deletion of USP9X in mice is embryonically lethal (64,65), and that USP9Y is probably expressed at much lower levels than USP9X, as assessed by the number of human/rat/mouse-expressed sequence tags presently available in the GenBank TM database (data not shown), the contribution of USP9Y for the hydrolysis of Ub-PEX5 in male animals, if any, is probably a minor one.…”

The Y chromosome-linked copy number variations and male fertility

“…In fact, Luddi et al (43) reported that this deletion has no effect on spermatogenesis and is thus compatible with fertility. On the other hand, previous studies (42,44,45) irrefutably demonstrate that the loss of the gene disturbs spermatogenesis to different degrees and that natural transmission is possible in case of a mild phenotype. Therefore, USP9Y has been proposed as a fine spermatogenic modulator (44), the absence of which is compatible with a highly variable phenotype probably linked to the genetic or other background of the carrier (42).…”