Disease relevance of ZFY

• We found expression of ZFY transcripts in 3 of 31 prostate adenocarcinomas by using Northern analysis [1].
• In 2 of the 6 benign prostatic hypertrophy (BPH) tissues analyzed by RT-PCR, barely detectable products of ZFY were observed, and none contained ZFX products [1].
• Recently, studies using reverse transcriptase polymerase chain reaction (RT-PCR) have detected paternal transcripts for the Y-linked genes, ZFY and SRY, and the myotonic dystrophy associated protein kinase gene, DK, as early as the late pronucleate one-cell stage [2].
• Previous investigations have shown that in other diseases and genes, most notably haemophilia B and A, but also the ZFY and ZFX genes, the male mutation rate for point mutations tends to be higher than the female one [3].
• To identify patients at risk of developing gonadoblastoma, a PCR based assay with SRY, ZFY and DYZ3 specific primers was carried out to detect different Y-sequences in the DNA of peripheral lymphocytes from patients with Turner's syndrome [4].

High impact information on ZFY

• ZFX has a gene structure similar to ZFY, the putative human sex determinant, and escapes X inactivation [5].
• ZFY and ZFX diverged from a common ancestral gene, as evidenced by similarities in their intron/exon organization and exon DNA sequences [5].
• The ZFY gene, located in the sex-determining region of the human Y chromosome, appears to encode a zinc-finger protein [6].
• The X,t(Y;22) female lacks the ZFY gene but does not exhibit the complex phenotype known as Turner's syndrome, arguing against the hypothesis that ZFY is the Turner's syndrome gene on the Y chromosome [7].
• Genetic evidence that ZFY is not the testis-determining factor [8].

Biological context of ZFY

• Recently, a candidate for the testis-determining gene (ZFY, Y-borne zinc-finger protein) has been cloned [9].
• In these individuals, the male phenotype could be explained by a mutation in a gene 'downstream' of ZFY in the sex-determining hierarchy; but in that case there should be no exchange of material between the X and Y chromosomes [8].
• Sequences homologous to ZFY, a candidate human sex-determining gene, are autosomal in marsupials [9].
• The ZFY probe detects a male-specific (Y-linked) sequence in DNA from a range of eutherian mammals, as well as an X-linked sequence (ZFX) which maps to the human X chromosome [9].
• We have isolated cDNA clones of ZFY and its homologue on the X chromosome, ZFX [10].

Anatomical context of ZFY

• Significantly, the 3-kb ZFY transcript was also detected in other mammalian adult testes [11].
• ZFY and ZFX are transcribed in a wide variety of XY and (in the case of ZFX) XX cell lines [5].
• None of the sample blanks showed any PCR product, all 90 of the karyotypically XY cells were correctly genotyped as ZFX/ZFY, all 83 of the 84 XX cells that amplified were correctly genotyped as ZFX only, and analyses of all same-embryo blastomeres were completely concordant (100% specificity) [12].
• Here we show that two Y-chromosomal genes involved in sex determination of the gonad, SRY and ZFY, are transcribed in hypothalamus, and frontal and temporal cortex of the adult male human brain [13].
• The patients' father (46, XY, no mosaicism detected in peripheral blood lymphocytes) was positive for SRY and ZFY sequences [14].

Associations of ZFY with chemical compounds

• Substitution of Phe by leucine in a ZFY peptide permits Zn(2+)-dependent folding [15].

Other interactions of ZFY

• Molecular genetics of sex determination in channel catfish: studies on SRY, ZFY, Bkm, and human telomeric repeats [16].
• In addition, since only female embryos inherit the paternal allele of X-linked G6PD, cDNA was also analyzed for ZFX/ZFY transcripts to identify the sex of each embryo [2].
• Following restriction digestion, paternal G6PD and ZFY transcripts were first detected at the four-cell stage and paternal ADA transcripts in an embryo at the three-cell stage coinciding with the onset of dependency on transcription from the embryonic genome [2].
• The SRY, PABY, and ZFY genes were present in all four patients [17].
• The zinc-finger proteins ZFX and ZFY, encoded by genes on the mammalian X and Y chromosomes, have been speculated to function in sex differentiation, spermatogenesis, and Turner syndrome [18].

Analytical, diagnostic and therapeutic context of ZFY

• Northern blot analysis of human foetal testis RNA has shown that three low abundance transcripts of 5, 6 and 8 Kb can be detected by ZFY-related DNA sequences [19].
• When we used reverse transcriptase PCR (RT-PCR) to analyze these same samples, the number of tumors expressing ZFY and/or ZFX transcripts increased to 20 of 31 [1].
• By in situ hybridization, we assigned ZFX and ZFY to human chromosome bands Xp21 and Yp11.3, respectively [20].
• An X-linked zinc finger gene mapping to Xq21.1-q21.3 closely related to ZFX and ZFY: possible origins from a common ancestral gene [21].
• Sequence analysis of the ZFY and Sox genes in the turtle, Chelydra serpentina [22].

References