Abstract
In a search for potential infertility loci, which might be revealed by clustering of chromosomal breakpoints, we compiled 464 infertile males with a balanced rearrangement from Mendelian Cytogenetics Network database (MCNdb) and compared their karyotypes with those of a Danish nation-wide cohort. We excluded Robertsonian translocations, rearrangements involving sex chromosomes and common variants. We identified 10 autosomal bands, five of which were on chromosome 1, with a large excess of breakpoints in the infertility group. Some of these could potentially harbour a male-specific infertility locus. However, a general excess of breakpoints almost everywhere on chromosome 1 was observed among the infertile males: 26.5 versus 14.5% in the cohort. This excess was observed both for translocation and inversion carriers, especially pericentric inversions, both for published and unpublished cases, and was significantly associated with azoospermia. The largest number of breakpoints was reported in 1q21; FISH mapping of four of these breakpoints revealed that they did not involve the same region at the molecular level. We suggest that chromosome 1 harbours a critical domain whose integrity is essential for male fertility.
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Acknowledgements
We are grateful to Prof. Patricia Jacobs, Wessex Region, Genetic Laboratory, UK for critical reading of the manuscript and for contributing unpublished cases. Jan Hansen and the Danish Cytogenetic Registry are acknowledged for data for the nation-wide cohort and Lene T Skovgaard and Peter Dalgaard, Department of Biostatistics, University of Copenhagen, Denmark for statistical assistance. We also thank Erik Niebuhr and Kirsten Fenger, Department of Medical Genetics, Institute of Medical Biochemistry and Genetics, University of Copenhagen, Denmark, for submitting unpublished cases and for advice regarding methods respectively. Wilhelm Johannsen Centre for Functional Genome Research was established by the Danish National Research Foundation, which funded this research.
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Bache, I., Assche, E., Cingoz, S. et al. An excess of chromosome 1 breakpoints in male infertility. Eur J Hum Genet 12, 993–1000 (2004). https://doi.org/10.1038/sj.ejhg.5201263
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DOI: https://doi.org/10.1038/sj.ejhg.5201263
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