Subject(s)
Chromosome Inversion/genetics , Spermatozoa/cytology , Cell Separation , Chromosome Banding , Humans , MaleABSTRACT
Paracentric inversions (PAI) are structural chromosomal rearrangements generally considered to be harmless. Nevertheless, cases of viable recombinants have been reported, indicating the interest of studying the meiotic behaviour of these chromosomal abnormalities. To date, the few studies reported have been performed using either the human-hamster fertilization system or fluorescence in situ hybridization with centromeric or telomeric DNA probes. In order to improve the assessment of meiotic segregation in PAI, we present a new strategy based on the use of bacterial artificial chromosome (BAC) probes which allow a precise localization of chromosome breakpoints and the identification of all meiotic products in human sperm. Sperm samples from carriers of an inv(5) and an inv(14) were used to test this new high-resolution procedure.
Subject(s)
Chromosome Breakage , Chromosome Inversion/genetics , Spermatozoa/metabolism , Chromosomes, Human, Pair 14 , Chromosomes, Human, Pair 5 , Humans , In Situ Hybridization, Fluorescence , Male , Meiosis/genetics , Models, GeneticABSTRACT
t(13;15) and t(14;15) are two rare Robertsonian translocations. Meiotic segregation was studied in four males heterozygous for the rare Robertsonian translocations t(13;15) and t(14;15). Both locus-specific probes (LSPs) and whole chromosome painting (WCP) probes, specific to chromosomes 13, 14 and 15, were used in this study. The number of spermatozoa scored for each carrier ranged from 891 to 5000. The frequencies of normal and balanced sperm resulting from the alternate mode of segregation ranged from 77.6 to 92.8%, confirming the prevalence of alternate segregation over other segregation modes in all Robertsonian translocations. The incidences of unbalanced complements ranged from 6.7 to 20.4%, with a significant excess of disomy rates over the complementary frequencies of nullisomy. This variability might reflect differences in the location of breakpoints in translocated chromosomes, leading to the variable production of unbalanced gametes and the variable alterations of semen parameters in Robertsonian translocation carriers.
Subject(s)
Chromosomes, Human, Pair 13 , Chromosomes, Human, Pair 14 , Chromosomes, Human, Pair 15 , In Situ Hybridization, Fluorescence/methods , Meiosis , Spermatozoa/ultrastructure , Translocation, Genetic , Adult , Chromosome Segregation , Heterozygote , Humans , MaleABSTRACT
Uniparental disomy (UPD) for several human chromosomes is associated with clinical abnormalities. We report the case of a 2-year-old boy with severe intrauterine and post-natal growth retardation (IUGR/PNGR) and highly variable sweat chloride concentrations. The patient was identified as heterozygous for the F508del mutation of the CFTR (cystic fibrosis transmembrane conductance regulator) gene. Unexpectedly, the signal corresponding to the maternally inherited F508del allele appeared much more intense than the paternally derived wild allele. Molecular analysis including polymorphic marker studies, microsatellites and single-nucleotide polymorphisms subsequently showed that the boy was a carrier of a de novo mosaic maternal isodisomy of a chromosome 7 segment while there was a biparental inheritance of the rest of the chromosome. This is the first report of a mosaic partial UPD7. The matUPD7 segment at 7q21-qter extends for 72.7 Mb. The karyotype (550 bands) of our patient was normal, and fluorescence in situ hybridization with probes mapping around the CFTR gene allowed us to rule out a partial duplication. The detection of this chromosomal rearrangement confirms the hypothesis that the 7q31-qter segment is a candidate for the localization of human imprinted genes involved in the control of IUGR and PNGR. It also emphasizes the importance of searching for UPD7 in severe, isolated and unexplained IUGR and PNGR.
Subject(s)
Chromosomes, Human, Pair 7/genetics , Fetal Growth Retardation/genetics , Genomic Imprinting/genetics , Uniparental Disomy/diagnosis , Uniparental Disomy/genetics , Alleles , Child, Preschool , Chlorides/analysis , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Humans , In Situ Hybridization, Fluorescence , Infant, Newborn , Infant, Small for Gestational Age , Male , Microsatellite Repeats/genetics , Mosaicism , Polymorphism, Single Nucleotide , Recombination, Genetic , Sweat/chemistryABSTRACT
BACKGROUND: The t(14;22) remains one of the rare Robertsonian translocations observed in human, with an occurrence estimated at 1.2%. Three cases of rare Robertsonian translocation t(14;22) were investigated for meiotic segregation in sperm samples from male carriers using the fluorescent in situ hybridization (FISH) procedure. The three carriers included two men with an abnormal semen analysis and one with normal semen parameters. METHODS: Both locus-specific probes and whole-chromosome painting probes, specific for chromosomes 14 and 22, were used in this study. The number of spermatozoa scored for each probe set ranged from 3279 to 10,024. RESULTS: In the three carriers, similar frequencies, ranging from 78.53 to 81.76%, were found for normal and balanced spermatozoa resulting from alternate segregation. The total proportion of unbalanced spermatozoa resulting from adjacent modes of segregation ranged from 17.59 to 20.94%. CONCLUSION: This finding confirmed the predominance of alternate segregation over other segregation types in all Robertsonian translocations and indicates a higher production of imbalances in the t(14;22) than in most of the Robertsonian translocations previously analysed. This could be related to the variable location of breakpoints in Robertsonian translocations. This breakpoint diversity could also play a role in the differences in reproductive status observed in male carriers of Robertsonian translocations.