title: Comprehensive meiotic segregation analysis of a 4-breakpoint t(1;3;6) complex chromosome rearrangement using single sperm array comparative genomic hybridization and FISH.
abstract: Complex chromosomal rearrangements (CCR) represent rare structural chromosome abnormalities frequently associated with infertility. In this study, meiotic segregation in spermatozoa of an infertile normospermic carrier of a 4-breakpoint t(1;3;6) CCR was analysed. A newly developed array comparative genomic hybridization protocol was used, and all chromosomes in 50 single sperm cells were simultaneously examined. Three-colour FISH was used to analyse chromosome segregation in 1557 other single sperm cells. It was also used to measure an interchromosomal effect; sperm chromatin structure assay was used to measure chromatin integrity. A high-frequency of unbalanced spermatozoa (84%) was observed, mostly arising from the 3:3 symmetrical segregation mode. Array comparative genomic hybridization was used to detect additional aneuploidies in two out of 50 spermatozoa (4%) in chromosomes not involved in the complex chromosome rearrangement. Significantly increased rates of diploidy and XY disomy were found in the CCR carrier compared with the control group (P < 0.001). Defective condensation of sperm chromatin was also found in 22.7% of spermatozoa by sperm chromatin structure assay. The results indicate that the infertility in the man with CCR and normal spermatozoa was caused by a production of chromosomally unbalanced, XY disomic and diploid spermatozoa and spermatozoa with defective chromatin condensation.
authors.affiliation: Central European Institute of Technology - Veterinary Research Institute, Hudcova 70, 621 00 Brno, Czech Republic; Repromeda, Centre for Assisted Reproduction, Vinicni 235, 615 00 Brno, Czech Republic. Electronic address: hornak@vri.cz.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Hornak
authors.affiliation: Central European Institute of Technology - Veterinary Research Institute, Hudcova 70, 621 00 Brno, Czech Republic.
authors.forename: Miluse
authors.initials: M
authors.lastname: Vozdova
authors.affiliation: Central European Institute of Technology - Veterinary Research Institute, Hudcova 70, 621 00 Brno, Czech Republic.
authors.forename: Petra
authors.initials: P
authors.lastname: Musilova
authors.affiliation: Central European Institute of Technology - Veterinary Research Institute, Hudcova 70, 621 00 Brno, Czech Republic.
authors.forename: Petra
authors.initials: P
authors.lastname: Prinosilova
authors.affiliation: Repromeda, Centre for Assisted Reproduction, Vinicni 235, 615 00 Brno, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Oracova
authors.affiliation: Repromeda, Centre for Assisted Reproduction, Vinicni 235, 615 00 Brno, Czech Republic.
authors.forename: Vlasta
authors.initials: V
authors.lastname: Linkova
authors.affiliation: Repromeda, Centre for Assisted Reproduction, Vinicni 235, 615 00 Brno, Czech Republic.
authors.forename: Katerina
authors.initials: K
authors.lastname: Vesela
authors.affiliation: Central European Institute of Technology - Veterinary Research Institute, Hudcova 70, 621 00 Brno, Czech Republic; Repromeda, Centre for Assisted Reproduction, Vinicni 235, 615 00 Brno, Czech Republic.
authors.forename: Jiri
authors.initials: J
authors.lastname: Rubes
mesh_terms: D000328:Adult; D056905:Chromosome Breakpoints; D020090:Chromosome Segregation; D055028:Comparative Genomic Hybridization; D018153:Czech Republic; D058490:Disorder of Sex Development, 46,XY / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D015321:Gene Rearrangement; D006579:Heterozygote; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007248:Infertility, Male / Q000209:etiology; D008297:Male; D049469:Meiotic Prophase I; D059010:Single-Cell Analysis; D013094:Spermatozoa / Q000473:pathology*; D014178:Translocation, Genetic
keywords: array CGH; complex chromosome rearrangement; interchromosomal effect; male infertility; meiotic segregation; sperm aneuploidy