Breakpoint mapping and complete analysis of meiotic segregation patterns in three men heterozygous for paracentric...

Paracentric inversions (PAIs) are structural chromosomal rearrangements generally considered to be harmless. To date, only a few studies have been performed concerning the meiotic segregation of these rearrangements, using either the human-hamster fertilization system or fluorescence in situ hybridization (FISH) with centromeric or telomeric DNA probes. To improve the assessment of imbalances in PAI, we present a new strategy based on FISH assay using multiple bacterial artificial chromosome probes, which allow a precise localization of chromosome break points and the identification of all meiotic products in human sperm. Sperm samples of three cases with PAI were investigated: an inv(5)(q13.2q33.1), an inv(9)(q21.2q34.13) and an inv(14)(q23.2q32.13). The frequencies of spermatozoa with inverted chromosomes were 44.7% in inv(5), 42.7% in inv(9) and 46.7% in inv(14). The global incidences of unbalanced complements were 9.7, 12.6 and 3.7% in inv(5), inv(9) and inv(14), respectively. This report is the first study providing a detailed description of meiotic segregation patterns in human sperm by using a sperm FISH approach. This study demonstrates that the detailed analysis of segregation in PAI may provide important data for both genetic analysis and counseling of inversion carriers.