1. ¹Wilhelm Johannsen Centre for Functional Genome Research, Department of Medical Biochemistry and Genetics, The Panum Institute, University of Copenhagen, Denmark
2. ²Centre for Medical Genetics and Reproductive Medicine, University Hospital, Dutch-speaking Free University of Brussels (Vrije Universiteit Brussel), Belgium
3. ^3–48Full affiliations can be seen as electronic supplement

Correspondence: Dr I Bache, Wilhelm Johannsen Centre for Functional Genome Research, IMBG, The Panum Institute, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen N, Denmark. Tel: +45 35327844; Fax: +45 35327845; E-mail: iben@medgen.ku.dk

⁴⁹These authors contributed equally to this work.

^†Claes Lundsteen died on 10th November 2003.

Received 27 February 2004; Revised 21 May 2004; Accepted 15 July 2004; Published online 15 September 2004.

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was observed both for translocation and inversion carriers, especially pericentric inversions, both for published and unpublished cases, and was significantly associated with azoospermia.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.