J Med Genet 1999;36:670-677 ( September )

The critical region of overlap defining the AZFa male infertility interval of proximal Yq contains three transcribed sequences

Carole A Sargent^a, Catherine A Boucher^a, Stefan Kirsch^b, Graeme Brown^a, Birgit Weiss^b, Anita Trundley^a, Paul Burgoyne^c, Neomie Saut^d, Christine Durand^d, Nicolas Levy^d, Philippe Terriou^d, Timothy Hargreave^e, Howard Cooke^f, Michael Mitchell^d, Gudrun A Rappold^b, Nabeel A Affara^a

^a Human Molecular Genetics Group, University of Cambridge, Department of Pathology, Tennis Court Road, Cambridge CB2 1QP, UK, ^b Ruprecht-Karls-Universitat Heidelberg, Institut fur Humangenetik, Im Neuenheimer Feld 328, 69120 Heidelberg, Germany, ^c National Institute for Medical Research, The Ridge Way, Mill Hill, London NW17 1AA, UK, ^d INSERM Genetique Medicale et Developpment, Faculte de Medecine de la Timone, 27 Boulevard Jean Moulin, 13385 Marseille Cedex 05, France, ^e Department of Urology and University of Edinburgh Department of Surgery (Urology), Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK, ^f MRC Human Genetics Unit, Department of Surgery (Urology), Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK

Correspondence to: Dr Affara.

Revised version received 11 May 1999; Accepted for publication 13 May 1999

The position of deletion breakpoints in a series of four AZFa male infertility patients has been refined using new markers derived from BAC clone DNA sequence covering the AZFa male infertility interval. The proximal half of the AZFa interval is occupied by pseudogene sequences with homology to Xp22. The distal half contains an anonymous expressed sequence tag (named AZFaT1) found transcribed in brain, testis, and skeletal muscle and the DFFRY and DBY genes. All the patients have AZFaT1 and DFFRY deleted in their entirety and three patients additionally have DBY deleted. The three patients with AZFaT1, DFFRY, and DBY deleted show a severe Sertoli cell only syndrome type I phenotype, whereas the patient that has retained DBY shows a milder oligozoospermic phenotype. The expression of DBY in a cell line from this latter patient is unaltered; this shows that it is the loss of genes lying within the deletion that is responsible for the observed oligozoospermia. RT-PCR analysis of mouse testis RNA from normal and XXSxr^a mice (devoid of germ cells) has shown that Dby is expressed primarily in somatic cells and that the level of expression is unaltered during germ cell differentiation. This contrasts with Dffry where no transcripts are detectable in XXSxr^a mouse testis and expression occurs specifically in testis mRNA in a germ cell dependent fashion.


Keywords: AZFa; Y chromosome; infertility

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© 1999 by J Med Genet
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