ORIGINAL ARTICLES

Phenotypic variation within European carriers of the Y-chromosomal gr/gr deletion is independent of Y-chromosomal background

C Krausz¹, C Giachini¹, Y Xue², M K O’Bryan³, J Gromoll⁴, E Rajpert-de Meyts⁵, R Oliva⁶, I Aknin-Seifer⁷, E Erdei⁸, N Jorgensen⁵, M Simoni^4,9, J L Ballescà¹⁰, R Levy¹¹, G Balercia¹², P Piomboni¹³, E Nieschlag⁴, G Forti¹, R McLachlan^14,15, C Tyler-Smith²

¹ Andrology Unit, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini, Florence, Italy
² The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK
³ Monash Institute of Medical Research and the Australian Research Centre of Excellence in Biotechnology and Development, Monash University, Clayton, Australia
⁴ Institute of Reproductive Medicine University of Münster, Münster, Germany
⁵ Department of Growth and Reproduction Copenhagen, University Hospital Rigshospitalet, Copenhagen, Denmark
⁶ Human Genetics Research Group, Biochemistry and Molecular Genetics Service, Hospital Clínic, Faculty of Medicine, University of Barcelona and IDIBAPS, Barcelona, Spain
⁷ Laboratoire de Biologie de la Reproduction, Pôle Mère Enfant, Laboratoire de Génétique et Biologie Moléculaire Section Molécules, Saint-Etienne, France
⁸ Andrology-Urology Division, National Health Center, Budapest, Hungary
⁹ University of Modena and Reggio Emilia Dept. of Medicine, Endocrinology, Metabolism and Geriatric, Modena, Italy
¹⁰ Institut Clínic of Gynecology, Obstetrics and Neonatology, Hospital Clínic, Barcelona, Spain
¹¹ Laboratoire d’Histologie Embryologie Cytogénétique Biologie de la Reproduction, France
¹² Division of Endocrinology, Institute of Internal Medicine Polytechnic University of Marche, Ancona, Italy
¹³ Deptarment of Surgery, Biology Section, University of Siena, Siena, Italy
¹⁴ Prince Henry’s Institute, Monash Medical Centre, Clayton, Australia
¹⁵ Monash IVF Pty Ltd, Richmond, Australia

Dr Csilla Krausz, Andrology Unit, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini, 6 Florence 50139, Italy; c.krausz{at}dfc.unifi.it

Background: Previous studies have compared sperm phenotypes between men with partial deletions within the AZFc region of the Y chromosome and non-carriers, with variable results. In this study, a separate question was investigated, the basis of the variation in sperm phenotype within gr/gr deletion carriers, which ranges from normozoospermia to azoospermia. Differences in the genes removed by independent gr/gr deletions, the occurrence of subsequent duplications or the presence of linked modifying variants elsewhere on the chromosome have been suggested as possible causal factors. This study set out to test these possibilities in a large sample of gr/gr deletion carriers with known phenotypes spanning the complete range.

Results: In total, 169 men diagnosed with gr/gr deletions from six centres in Europe and one in Australia were studied. The DAZ and CDY1 copies retained, the presence or absence of duplications and the Y-chromosomal haplogroup were characterised. Although the study had good power to detect factors that accounted for 5.5% of the variation in sperm concentration, no such factor was found. A negative effect of gr/gr deletions followed by b2/b4 duplication was found within the normospermic group, which remains to be further explored in a larger study population. Finally, significant geographical differences in the frequency of different subtypes of gr/gr deletions were found, which may have relevance for the interpretation of case control studies dealing with admixed populations.

Conclusions: The phenotypic variation of gr/gr carriers in men of European origin is largely independent of the Y-chromosomal background.

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