title: Detection of structural abnormalities in spermatozoa of a translocation carrier t(3;11)(q27.3;q24.3) by triple FISH.
abstract: Structural chromosome abnormalities in spermatozoa represent an important category of paternally transmittable genetic damage. A couple was referred to our centre because of repetitive abortions and the man was found to be a carrier of a reciprocal translocation t(3;11)(q27.3;q24.3). A tailored fluorescence in situ hybridisation (FISH) approach was developed to study the meiotic segregation patterns in spermatozoa from this translocation carrier. A combination of three DNA probes was used, a centromeric probe for chromosome 11, a cosmid probe for chromosome 11q and a YAC probe for chromosome 3q. The frequency of spermatozoa carrying an abnormal chromosome constitution was compared with baseline frequencies in control semen specimens and it was found that a significantly higher percentage of spermatozoa carried an abnormal constitution for the chromosomes involved in the translocation. A normal or balanced chromosome constitution was found in 44.3% of the analysed spermatozoa, while the remainder exhibited an abnormal chromosome constitution reflecting different modes of segregation (15.9% adjacent I segregation, 6.5% adjacent II segregation, 28.9% 3:1 segregation, 0.8% 4:0 segregation, 3.6% aberrant segregation). The frequency of aneuploidy for chromosomes X, Y, 13 and 21 was assessed using specific probes but there was no evidence of interchromosomal effects or variations in the sex ratio in spermatozoa from the translocation carrier. In conclusion, structural aberrations can be reliably assessed in interphase spermatozoa using unique DNA probe cocktails, and this method provides insight into the genetic constitution of germ cells and enables evaluation of potential risks for the offspring.
authors.affiliation: Department of Molecular Cell Biology and Genetics, University of Maastricht, The Netherlands. Elena.Martini@molcelb.unimaas.nl
authors.forename: E
authors.initials: E
authors.lastname: Martini
authors.forename: A R
authors.initials: AR
authors.lastname: von Bergh
authors.forename: E
authors.initials: E
authors.lastname: Coonen
authors.forename: C E
authors.initials: CE
authors.lastname: de Die-Smulders
authors.forename: A H
authors.initials: AH
authors.lastname: Hopman
authors.forename: F C
authors.initials: FC
authors.lastname: Ramaekers
authors.forename: J P
authors.initials: JP
authors.lastname: Geraedts
mesh_terms: D000328:Adult; D002869:Chromosome Aberrations / Q000235:genetics / Q000473:pathology; D025063:Chromosome Disorders; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008540:Meiosis / Q000235:genetics; D015335:Molecular Probes; D013094:Spermatozoa / Q000002:abnormalities*; D014178:Translocation, Genetic / Q000235:genetics*; D014960:X Chromosome / Q000235:genetics; D014998:Y Chromosome / Q000235:genetics
chemical_list: D015335:Molecular Probes