Can one translocation impact the meiotic segregation of another translocation? A sperm-FISH analysis of a 46,XY,t(1;16)(q21;p11.2),t(8;9) (q24.3;p24) patient and his 46,XY,t(8;9)(q24.3;p24) brother and cousin (original) (raw)
Related papers
Meiotic segregation analysis of reciprocal translocations both in sperms and blastomeres
American Journal of Medical Genetics Part A, 2006
Balanced chromosomal rearrangements could lead to unbalanced segregation gametes during meiosis. In this study, sperm flourescence in situ hybridization (FISH) analysis of meiotic segregation products of four reciprocal translocations; 46,XY,t(7;10)(q21;q22), 46,XY,t(15;17)(q11;p12), 46,XY,t(6;13)(p21.1;q32), and 46,XY,t(1;13)(q24;q10) are presented. In three out of these four cases with t(15;17), t(6;13), and t(1;13) additional blastomere FISH analyses are also provided. Multi-color FISH analysis was applied using diverse probe combinations specific for translocated chromosome segments. The average frequency of sperm nuclei bearing unbalanced products for t(7;10), t(15;17), t(6;13), and t(1;13) were 48.7%, 59.5%, 60.5%, and 62.9%, respectively. Frequencies of blastomeres comprising unbalanced products in cases with t(15;17), t(6;13), and t(1;13) were 80% (12 of 15), 60% (3 of 5), and 50% (2 of 4), respectively. Chi-square test analysis showed significant differences in the meiotic segregation patterns due to the distribution and numbers of the chiasmatas that could depend on the size of the translocated segments (P < 0.001). In conclusion, FISH analysis of sperm and blastomere for reciprocal translocation carriers effectively estimates the approximate risk of unbalanced products and this result might ensure valuable genetic counseling. © 2006 Wiley-Liss, Inc.
Meiotic segregation of translocations during male gametogenesis
International Journal of Andrology, 2004
Balanced reciprocal and Robertsonian translocations are the most common structural chromosomal abnormalities in humans. Generally, they are without consequence for the carrier, but for various degrees of oligoasthenoteratozoospermia in men. As these carriers can produce a significant percentage of gametes with an unbalanced combination of the parental rearrangement, there is a more or less significant risk, according to cases, of chromosomal imbalances for their offspring. Therefore, techniques were developed to study the meiotic segregation of these translocations in males. Direct investigation of human sperm chromosomes became possible by karyotyping spermatozoa after penetration of zona-free hamster oocytes and, more recently, using fluorescent in situ hybridization (FISH). This paper reviews the results obtained using these techniques in Robertsonian and reciprocal translocations. The studies on spermatozoa from translocation carriers help the comprehension of the mechanisms of the meiotic segregation. They should be integrated in the genetic exploration of the infertile men, in order to give them a personalized risk assessment of unbalanced spermatozoa, specially as a correlation was found recently between the percentage of abnormal spermatozoa and that of abnormal embryos.
Meiotic and sperm chromosome studies in a reciprocal translocation t(1;2)(q32;q36)
Human Genetics, 1990
Meiotic and sperm chromosomes were studied in a man heterozygous for a reciprocal translocation t(1;2)(q32; q36). Forty-five meiotic metaphase I cells were obtained from semen samples: 86.6% were 22,XY,IV and 13.3% had synaptic anomalies that affected all or some of the bivalents. The quadrivalents observed had a ring configuration (92.3%) or a chain configuration (7.7%). A total of 105 sperm chromosome complements were analyzed: 41% resulted from an alternate segregation, and the percentage of unbalanced sperm was 59%; most of them (71%) resulted from an adjacent 1 segregation. The frequency of anomalies unrelated to the translocation (5.7% numerical and 14.1% structural anomalies) were within the normal range for control donors. There was a good correspondence between the percentage of cells with a ring IV (92.3%) and the proportion of 2:2 segregations (88.6%) and between the percentage of chain IV (7.7%) and the incidence of 3:1 segregations (11.4%).
From spermatocytes to sperm: meiotic behaviour of human male reciprocal translocations
Human Reproduction, 2004
BACKGROUND: Human male translocation carriers may present alterations in the meiotic process due to the presence of the translocated chromosomes. The aim of this work was to study the mechanisms that affect meiotic segregation in translocation carriers by analysing different stages of the meiotic process. METHODS: Meiotic studies using fluorescence in-situ hybridization on both spermatocytes and sperm nuclei were performed in two translocation carriers, t(11;17)(q13.1;p11.2) and t(10;14)(q24;q32). RESULTS: A ring configuration was the main type of quadrivalent found in metaphase I. Overall chiasma frequency was significantly decreased in the t(11;17) carrier. In the t(10;14) carrier, chiasma frequency within the interstitial region of chromosomes 10 and 14 was increased and the recombination pattern was modified. As expected from the frequencies of interstitial chiasmata found in metaphase I in the two subjects, the incidence of asymmetric dyads was sporadic in t(11;17) and very high in t(10;14). In both carriers, segregation frequencies observed at metaphase II were not different from the segregation data obtained in decondensed sperm nuclei. CONCLUSIONS: The concordance observed among results obtained in different spermatogenic stages indicates an absence of cellular selection based on chromosomal imbalances. Results obtained in the aneuploidy assay have not provided any evidence for an interchromosomal effect.
Journal of Andrology, 2006
Reciprocal chromosomal translocations (RCT) have long been recognized as important etiological factors in reproductive failure. In the present study, the meiotic segregation patterns of the spermatozoa of two related t(4;5)(p15.1;p12) carriers (proband and his father) were compared to the empirical data from a three-generation pedigree for risk assessment. Cytogenetic analysis of the metaphase chromosomes was performed, and triple color fluorescence in situ hybridization (FISH) was applied to the sperm heads. Similar patterns of meiotic segregation were observed for both carriers, despite the finding of teratozoospermia in the proband but not in his father. In addition, an increase of aneuploidy in chromosome 15 in the proband and aneuploidy of chromosomes X and Y in the father were observed. The high rate of miscarriages (6/10 pregnancies and 4/7 pregnancies after ascertainment correction) in this family could be explained by the genetically unbalanced karyotype and fertilization mediated by the unbalanced spermatozoa observed for both men at a frequency of more than 60%. The risk assessment for unfavorable pregnancy outcomes was predicted as 1.6% for unbalanced progeny at birth and about 30% for miscarriage. These figures may be used as guidelines for the genetic counseling of families with similar RCT.
Human Reproduction, 2008
BACKGROUND: Balanced translocations are associated with infertility, spontaneous abortions and birth defects. METHODS: We report the analysis, by multicolour fluorescence in situ hybridization (FISH), of meiotic segregation and aneuploidy of chromosomes X, Y, 7, 8 and 21 in sperm from three men who are carriers of two different translocations involving chromosomes 11 and 18. A control group comprised ten young, healthy normospermic men. RESULTS: the higher prevalence of alternate segregation followed by adjacent 1, adjacent 2 and 3:1, and other segregants was observed in all three patients. Two carriers of the same translocation differed only in the frequency of adjacent 2 segregation (P < 0.01). The carrier of the other translocation showed significantly higher frequency of alternate (P < 0.01) and less adjacent 1 and 3:1 segregation products (P < 0.01). An increased frequency of XY (P < 0.01), YY (P < 0.05) and diploid (P < 0.01) sperm was also detected in the group of translocation carriers compared with the control group. This difference was caused by elevated frequencies of disomy and diploidy in two of our carriers. CONCLUSIONS: the incidence of chromosomally unbalanced or aneuploid gametes varies in the individual translocation carriers even if the same chromosomes are included in the translocation. FISH analysis provides information useful for genetic counseling and assisted reproduction.
Human Reproduction, 2010
background: Human translocation carriers may present alterations in meiosis. Understanding the mechanism of meiotic segregation of reciprocal translocations is important for estimation of the risk of either pregnancy loss or birth defects. The objective of this work was to estimate meiotic segregation rates in preimplantation embryos from preimplantation genetic diagnosis (PGD) cycles of female and male reciprocal translocation carriers. methods: In 20 cycles for 14 couples, PGD was performed on 118 day three embryos using fluorescence in situ hybridization (FISH) with specific probes for each translocation. The meiotic segregation modes and the effect of the paternal origin of translocated carrier were estimated. results: Overall, the proportions of alternate segregation for normal or balanced chromosome contents in preimplantation embryos from PGD cycles in reciprocal male and female carriers were not significantly different (35.5 versus 23.8%). However, the frequencies of adjacent-1 and adjacent-2 segregation were lower in embryos from female reciprocal translocation carriers than from male carriers. For male translocations, alternate segregation was the most frequent mode. The proportion of 3:1 segregation was the most frequent in female translocations carriers. conclusions: We report differences in segregation modes in embryos obtained from PGD cycles according to the gender of reciprocal translocation carrier. However, these differences did not affect the proportion of balanced embryos and the take home baby rate. The analysis of the meiotic behaviour of chromosomes and the differences between the meiotic products of female and male for a chromosomal rearrangement could help predict the outcome of PGD for translocation carriers.
Fertility and Sterility, 2011
Objective: To directly study the meiotic segregation of a complex reciprocal translocation (CCR) as well as the occurrence of an interchromosomal effect. Design: In situ sperm fluorescence in situ hybridization (FISH) analysis. Setting: Department of Cytogenetics and INSERM research center. Patient(s): A male carrier of a balanced complex reciprocal translocation t(5;13;14)(q23;q21;q31). Intervention(s): Sperm samples from the carrier and direct FISH analysis on sperm slide preparations. Main Outcome Measure(s): Meiotic segregation pattern determined on sperm nuclei and estimation of the incidence of unbalanced spermatozoa and an interchromosomal effect (ICE).
European Journal of Human Genetics, 2001
Meiotic segregation of a t(4;8)(q28;p23) translocation carrier was determined by two different methods to compare the final results. A total of 352 sperm chromosome complements, obtained after human-hamster in vitro fertilisation, were analysed by whole chromosome painting, and 6590 sperm heads were studied by fluorescence in situ hybridisation (FISH). Frequencies of alternate, adjacent I, adjacent II and 3 : 1 segregations were, for sperm chromosomes, 35.5, 33.2, 19.9 and 11.3% respectively. For sperm head analysis, results were 30.5, 28.5, 20.5 and 19.5% respectively. There were no statistically significant differences between the two methods with respect to the observed frequencies of sperm with balanced and unbalanced chromosome constitutions. Among unbalanced gametes, the methods differed only in the frequency of 3 : 1 segregation (w 2 , P50.0001). Different factors that could explain this result are discussed. To determine possible interchromosomal effects, multicolour FISH was used on sperm heads. Disomy rates of sex and 18 chromosomes were higher in the translocation carrier than in the control. The differences observed were statistically significant (P50.0001 for chromosomes X and 18, and P=0.0091 for chromosome Y). European Journal of Human Genetics (2001) 9, 395 ± 403.