Meiotic segregation analysis in sperm of a pericentric inversion of chromosome 19 heterozygous carrier: assessment of recombination frequency and genetic risk.

Introduction: Pericentric inversions (PEI) are rare intrachromosomal balanced structural abnormalities. To achieve complete synapsis and recombination during meiosis, the pairing of normal and inverted chromosomes requires the formation of an inversion loop. A crossover within this inversion loop leads to the production of two complementary recombinant chromosomes, which may contain both duplicated and deleted segments, including regions distal to the inversion. The clinical relevance of inverted chromosomes is significant, as they can result in the generation of recombinant gametes that may lead to early miscarriages, stillbirths, or congenital abnormalities in the progeny of carriers. The empirical frequencies of recombinant spermatozoa in men heterozygous for inv(19)(p13.3q12) were estimated. Additionally, the presence of the interchromosomal effects (ICE) on chromosomes 13, 18, 21, X, and Y was evaluated.

Methods: Fluorescence in situ hybridization (FISH) was performed on sperm nuclei using DNA probes for the subtelomeric regions of the short (p-) and long (q-) arms of chromosome 19, the centromeric regions of chromosome18, X, and Y as well as DNA probes for the regions 13q14 and 21q22.

Results: The inverted segment on chromosome 19 measures 31.5 Mb, which represents 53.3% of the total length of the affected chromosome. FISH analysis of 2,923 sperm nuclei revealed no detection of recombinant chromosomes. ICE on chromosomes 13, 18, 21, X, and Y were not observed.

Conclusion: Empirical data have been obtained for the first time regarding the frequency of gametes containing recombinant chromosomes, as well as the absence of interchromosomal effects on chromosomes 13, 18, 21, X, and Y during the meiotic segregation of the pericentric inversion of chromosome 19, inv(19)(q13.3q12). It was demonstrated that the extremely low risk of recombinant chromosome formation, falling below the detectable threshold (with 95% confidence intervals), is associated with inv(19)(p13.3q12). We hypothesize that the meiotic behavior of pericentric inversions is influenced not only by the relative size of the inverted segment but also by the morphological characteristics of the affected chromosome. Further studies are needed to explore the factors that influence the meiotic behavior of pericentric inversions.