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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


<ul><li><p>THE RELATIONSHIP BETWEEN DAZ &amp; MALE INFERTILITY</p></li><li><p>IntroductionY nonrecombining 10 testis DAZ gene family Yq11 interval 6 4 copy deletion .</p><p> DAZ complementary DNAs spermatogenesis testis .</p><p>Subfertile infertile conventional PCR techniques DAZ gene 4 deletion . </p><p> gene-specific PCR digestion assay 4 DAZ gene sequence family variants . </p><p> DAZ genes 4 deletion azoospermia svere oligozoospermia .</p></li><li><p>Material &amp; MethodsPatients and Semen Donors1997 1998 139 subfertility infertility </p><p>Conventional PCR AssaysLeukocytes DNA PCR amplification Deletions loci : sY81, sY84, sY182, sY94, sY102, sY117, sY143, sY147 sY152, sY153, and sY157.</p><p>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. </p><p>Statistical Analysist-test </p></li><li><p>Results</p></li><li><p>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 </p><p>4. 4 . DAZ . 4 DAZ RNA recognition motifs . . </p><p>5. clusters . less severe phenotype cluster DAZ . cluster1 cluster2 .</p><p>6. DAZ gene cluster 6 3 sperm 5 X 106 cells/mL . deletions deletion .</p></li><li><p>References1. B.T. Lahn and D.C. Page , Functional coherence of the human Y chromosome. Science 278 (1997), pp. 675680</p><p>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. </p><p>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. </p><p>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</p><p>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.</p><p>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. </p><p>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. </p><p>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. </p></li></ul>