• View

  • Download

Embed Size (px)


THE RELATIONSHIP BETWEEN DAZ & MALE INFERTILITY. Fertil Steril 2002 Jan;77(1):68-75 Reduced copy number of DAZ genes in subfertile and infertile men - PowerPoint PPT Presentation



  • IntroductionY nonrecombining 10 testis DAZ gene family Yq11 interval 6 4 copy deletion .

    DAZ complementary DNAs spermatogenesis testis .

    Subfertile infertile conventional PCR techniques DAZ gene 4 deletion .

    gene-specific PCR digestion assay 4 DAZ gene sequence family variants .

    DAZ genes 4 deletion azoospermia svere oligozoospermia .

  • Material & MethodsPatients and Semen Donors1997 1998 139 subfertility infertility

    Conventional PCR AssaysLeukocytes DNA PCR amplification Deletions loci : sY81, sY84, sY182, sY94, sY102, sY117, sY143, sY147 sY152, sY153, and sY157.

    FISH sequenced DAZ cosmids FISH probes . DAZ 5 Cosmid 18E8 (Genbank AC010089) exons 2 11 Cosmos 63C9 (Genbank AC000021) exons 2 11 35 kb downstream DAZ 3 Cosmid 46A6 (Genbank AC000022) 18E8 46A6 combination probes DAZ gene 5 3 detection 18E8 63C9 combination of probes 5 single clusters DAZ gene detection Fiber FISH .Probe biotin digoxigenin labeling, target DNA avidin antidigoxigenin antibodies fluorochromes Cy3 (red) fluorescein (green) hybridization detectecting.

    Statistical Analysist-test

  • Results

  • Discussion1. Y DAZ gene 3 autosomal DAZL transposition . Intragenic amplification, exon pruning duplication Y head-to-head manner 4 .2. sY581 marker exons 2 6 DAZ gene 10.8-kb segment detect probes . region RNA recognition motif DAZ gene clusters motif 7 .: DAZ1 , DAZ4 , DAZ2 DAZ3 .3. partial deletions DAZ gene clusters . AZFb deletion cluster 1 Y deletion . cluster 1 AZFb cluster cluster 2 cluster . AZFb deletion AZFc deletion . breakpoints overlap , intervals

    4. 4 . DAZ . 4 DAZ RNA recognition motifs . .

    5. clusters . less severe phenotype cluster DAZ . cluster1 cluster2 .

    6. DAZ gene cluster 6 3 sperm 5 X 106 cells/mL . deletions deletion .

  • References1. B.T. Lahn and D.C. Page , Functional coherence of the human Y chromosome. Science 278 (1997), pp. 675680

    2. J. Prosser, J.D. Inglis, A. Condie, K. Ma, S. Kerr, R. Thakrar et al., Degeneracy in human multicopy RBM (YRRM), a candidate spermatogenesis gene. Mamm Genome 7 (1996), pp. 835842.

    3. N.N. Chai, H. Zhou, J. Hernandez, H. Najmabadi, S. Bhasin and P.H. Yen , Structure and organization of the RBMY genes on the human Y chromosome: transposition and amplification of an ancestral autosomal hnRNPG gene. Genomics 49 (1998), pp. 283289.

    4. R. Saxena, J.W.A. de Vries, S. Repping, R.K. Alagappan, H. Skaletsky, L.G. Brown et al., Four DAZ genes in two clusters found in the AZFc region on the human Y chromosome. Genomics 67 (2000), pp. 256267

    5. H.Y. Yen , A long-range restriction map of deletion interval 6 of the human Y chromosome: a region frequently deleted in azoospermic males. Genomics 54 (1998), pp. 512.

    6. B. Glaser, P.H. Yen and W. Schempp , Fibre-fluorescence in situ hybridization unravels apparently seven DAZ genes or pseudogenes clustered within a Y-chromosome region frequently deleted in azoospermic males. Chromosome Res 6 (1998), pp. 481486.

    7. A.I. Agulnik, A. Zharkikh, H. Boettger-Tong, T. Bourgeron, K. McElreavey and C.E. Bishop , Evolution of the DAZ gene family suggests that Y-linked DAZ plays little, or a limited, role in spermatogenesis but underlines a recent African origin for human populations. Hum Mol Genet 7 (1998), pp. 13711377.

    8. A.E. Calogero, M.R. Garofalo and R. D'Agata , Factors influencing the variable incidence of Y chromosome microdeletions in infertile patients. Hum Reprod 14 (1999), p. 275.