Hum. Reprod. Advance Access originally published online on January 26, 2006
Human Reproduction 2006 21(5):1166-1171; doi:10.1093/humrep/dei477
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Meiotic segregation of rare Robertsonian translocations: sperm analysis of three t(14q;22q) cases
1 Institute of Human Genetics, CNRS, 2 Department of Medical Genetics, CHU Montpellier, France, 3 Department of Medical Genetics, School of Medical Sciences, Tarbiat Modarres University, Tehran, Iran, 4 Laboratory of Cytogenetics, 5 Laboratory of Biology of the Development and the Reproduction, CHU Clermont-Ferrand and 6 Laboratory of Biology of the Reproduction, CHU Montpellier, France
7 To whom correspondence should be addressed at: CNRS UPR 1142, Institute of Human Genetics, 141 rue de la Cardonille, F-34396 Montpellier Cedex 5, France. E-mail: franck.pellestor{at}igh.cnrs.fr
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and methodsResultsDiscussionAcknowledgementsReferences |
|---|
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.
Key words: FISH/imbalance/meiotic segregation/Robertsonian translocation/sperm
|
Introduction |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionAcknowledgementsReferences |
|---|
The t(14;22) constitutes one of the less frequent, non-homologous Robertsonian translocations found in humans. This rare structural rearrangement accounts for only 1.2% of all detected Robertsonian translocations (Therman et al., 1989
; Gardner and Sutherland, 2004). The few cases of t(14;22) reported were ascertained through infertility, unspecific mental retardation or by chance in newborn surveys and amniocenteses (Boue and Gallano, 1984; Therman et al., 1989; Guichaoua et al., 1990).
Like other Robertsonian translocations, the meiotic segregation of the t(14;22) can occur through either alternate segregation producing normal and balanced gametes or adjacent segregations leading to unbalanced gametes. In men heterozygous for Robertsonian translocations, the sperm chromosomal analysis provides a direct approach for determining the meiotic segregation pattern of translocated chromosomes and assessing the chance of having a normal conceptus. To date, most of these sperm studies, using the technique of in vitro sperm fertilization of hamster eggs, the microinjection of human spermatozoa into mouse oocytes or the fluorescent in situ hybridization (FISH) method, have focused on the most frequent Robertsonian translocations, i.e. the t(13;14) and the t(14;21), with 18 and 6 cases studied, respectively (Morel et al., 2004). Only three cases of rare Robertsonian translocations, i.e. t(13;15), t(15;22) and t(21;22), were investigated using the hamster egg fertilization system (Pellestor, 1990; Martin et al., 1992; Syme and Martin, 1992). More recently, fluorescence in situ hybridization (FISH) analyses were performed in the sperm of the carrier of a homologous t(21;21) Robertsonian translocation (Acar et al., 2002), a t(13;15) (Rives et al., 2005) and for the carrier of a t(13;22) (Anahory et al., 2005). All these studies have shown the strong prevalence of alternate segregation in gametes of male carriers, but they have also indicated the existence of significant heterogeneity in the rates of unbalanced gametes, varying from 2.7 to 26.5% according to the translocations.
To improve our understanding of the meiotic behaviour of rare Robertsonian translocations, and to provide adequate information and reproductive counselling for carriers of such structural chromosomal rearrangements, we have analysed the meiotic segregation in sperm from three subjects heterozygous for the rare Robertsonian translocation t(14;22).
|
Materials and methods |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionAcknowledgementsReferences |
|---|
Patients
Three unrelated men heterozygous for the t(14;22) and consulting for infertility were included in this study. The three patients were informed of the investigations planned, and they signed a consent form before participation in this study, which was approved by the ethical board of the CNRS and the Montpellier University Hospital.
Donor A, aged 37 years, was diagnosed with a t(14;22) after 5 years of sexual intercourse without conception. Physical examination and sexual development were normal, but the subject displayed oligoasthenoteratozoospermia (OAT) (sperm count: 13 x 106/ml, 50% normal morphology and 30% progressive motility). His wife was healthy with a normal karyotype. The couple had undergone four assisted reproduction technique (ART) cycles including one IVF attempt and three ICSIs, without pregnancy.
Patient B, aged 30 years, was ascertained through a fertility workup after 2 years of infertility. Semen analysis revealed teratospermia (sperm count: 31 x 106/ml, 30% normal morphology and 50% progressive motility). His wife had severe endometriosis with no hope of assisted reproduction procedure.
Patient C, aged 34 years, was ascertained through systematic sperm donor screening for artificial insemination by donor. He had one normal child and one heterozygous for the translocation. His semen analysis was normal with a sperm count of 77x106/ml, 70% with normal morphology and 65% with progressive motility.
A sperm sample from a fertile, 33 year-old man with normal seminal parameters and a normal karyotype was used as a control.
Sperm preparation
Sperm samples were processed as previously described (Anahory et al., 2005). Each sample was washed three times in x1 phosphate-buffered saline (PBS) by centrifugation (300g, 5 min) and fixed for 1 h in fresh fixative (3 : 1 methanol : glacial acetic acid) at –20°C. The sperm suspension was then dropped onto clean microscope slides and air dried. Slides were aged 2 days at room temperature before use for in situ chromosomal labelling.
Before FISH procedure, the slides were immersed for 10 min in a pepsin solution (50 ng/ml in 0.01M HCl) pre-warmed at 37°C, washed 2 min in x1 PBS and then dehydrated through an ethanol series (70, 90 and 100%) and air dried. The sperm nucleus decondensation and DNA denaturation were performed by slide incubation in 0.5M NaOH solution at RT for 8 min, followed by a wash in x2 saline sodium citrate (SSC), dehydration through an ethanol series and immersion in 70% formamide/x2 SSC solution 3 min at 73°C. Finally, the slides were washed in x2 SSC, dehydrated through an ethanol series and air dried.
FISH procedure
Two types of probes were used in this study. The first probe mixture was composed of locus-specific probes (LSP) derived from BAC and PAC clones and used in contig as indicated in Table I. All specific probes were mixed equally and labelled by nick-translation, using either Spectrum Orange or Spectrum Green (Vysis, Downers Grove, IL, USA) and then diluted in a 10 µl hybridization mix (50% formamide/50% dextran sulphate). The second probe mixture consisted of commercial whole-chromosome painting probes (WCP) from Vysis, including a chromosome 14 painting probe (WCP 14) labelled with Spectrum Green and a chromosome 22 painting probe (WCP 22) labelled with Spectrum Orange. The probes were prepared according to the manufacturer’s instructions.
|
Both LSP and WCP were denatured separately for 7 min at 75°C in a water bath and were left for pre-annealing in a water bath at 37°C for 15 min. Each probe mix was applied to the denatured slides, and slides were covered with coverslips, sealed with rubber cement and hybridized overnight in a dark, moist chamber at 37°C. After hybridization, coverslips were gently removed, and the slides were washed twice in 50% formamide/50% x2 SSC solution at 45°C, then twice in x2 SSC at 45°C and finally mounted with DAPI, 4',6-Diamidino-2-phenylindole, (100 ng/ml) in antifade solution. The slides were analysed by two independent observers using a Leitz fluorescence microscope DMRA2 equipped with a filter set for FITC, Texas Red, Aqua and DAPI/Texas Red/FITC.
Only individual and well-delineated sperm nuclei were scored. The scoring criteria were similar for LSI and WCP probes. Briefly, overlapping sperm nuclei, disrupted nuclei or large nuclei with diffuse signals were not considered. Sperm nuclei were scored as having two identical signals when the two spots were of equal size and intensity and were separated by at least the diameter of one hybridization domain.
Data analysis
The 
2 test was used to statistically analyse the segregation patterns observed in patients and compare the fluorescent phenotypes between the translocation carriers and the control subjects, as well as to compare results between the two types of labelling procedures. Both Student’s t-test and the non-parametric Mann–Whitney U-test were used to verify the homogeneity of segregation data between LSP and WCP assays. Differences were considered to be significant when P < 0.05.
|
Results |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionAcknowledgementsReferences |
|---|
The labelling efficiency of both LSP and WCP was determined on lymphocyte preparations and sperm preparations from the control donor. The hybridization efficiency values ranged from 99.1 to 99.8% according to the probes. There was no significant difference (P > 0.05) in hybridization efficiency between the two types of probes.
A total of 29 865 sperm nuclei from the three translocation carriers and 14 797 from the control were analysed for this study. The results of the segregation analysis are detailed in Table II.
|
The incidence of normal and balanced sperm (Figure 1A, C and F) nuclei resulting from alternate segregation was similar (P > 0.05) in the three patients, ranging from 78.53 to 81.76%. The global rate of unbalanced spermatozoa resulting from adjacent segregation modes ranged from 17.59 to 20.94% (Figure 1A–E). In each patient, the distribution of unbalanced patterns was similar in both the LSP and WCP assays, as indicated by the Student’s t-test (P > 0.90) and the non-parametric Mann–Whitney U-test (U > 5; P > 0.1). In the three patients, the incidences of disomy for both chromosomes 14 and 22 were higher than the complementary frequencies of nullisomy. The differences reached a significant level (P < 0.05) in all LSP assays, but only in three WCP experiments (chromosome 14 nullisomy : disomy ratio in patients A and B; chromosome 22 nullisomy : disomy ratio in patient C). However, detailed statistical analysis indicated significant variations (P < 0.05) between LSP and WCP results in patient A for the disomy 14 rate and in patients B and C for the disomy 22 rate. The incidence of sperm nuclei with a fluorescent pattern corresponding to either 3 : 0 segregation or diploid spermatozoa ranged from 0.33 to 0.79%.
|
The mean frequencies of disomies 14 and 22 in the sperm sample from the control were 0.15 and 0.21%, respectively, and the mean rate of nullisomy was estimated at 0.12% for chromosome 14 and 0.21% for chromosome 22. The frequency of diploid spermatozoa in this subject was 0.17%.
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionAcknowledgementsReferences |
|---|
The present study is the first report on the meiotic segregation in male carriers of rob(14;22). The only available data on the meiotic behaviour of this rare structural rearrangement came from the pachytene analysis performed in an oligospermic man heterozygous for a t(14;22) (Guichaoua et al., 1990
) and from the ultrastructural and chromosomal analyses carried out in another sterile male carrier of a 14;22 translocation (Baccetti et al., 2002). Both these studies identified structural and genomic defects associated with the translocation in germinal cells. Unfortunately, the sperm chromosome analysis performed by Baccetti et al. (2002) concerned only chromosomes 18, X and Y and consequently was not informative on the meiotic segregation of the t(14;22).
Despite its rarity and the fact that the potential trisomies 14 and 22 are expected to end in miscarriage, the translocation t(14;22) is interesting because of the predominant association of translocations involving chromosome 14 with male infertility (Therman et al., 1989) and the implication of chromosome 14 in uniparental disomy (UPD). Maternal and paternal UPD for chromosome 14 result in distinct abnormal phenotypes due to imprinted genes (Sutton and Shaffer, 2000). The phenotype associated with paternal UPD 14 may be severe, producing mental retardation and dysmorphism (Kotzot and Utermann, 2005). Postzygotic correction of a trisomy through mitotic loss of one of the free homologues is considered as the most likely mechanism for UPD, although monosomy rescue and gametic complementation may occur as well (Spence et al., 1988). The risk of UPD 14, estimated for common rob(13;14) and rob(14;21), is around 0.5% (Silverstein et al., 2002). This risk estimate is in the range of risk for aneuploidy in prenatal diagnosis. However, in rare Robertsonian translocations involving chromosomes 14 or 15, a greater incidence of UPD cannot be excluded (Gardner and Sutherland, 2004).
We have studied the meiotic segregation pattern in three carriers of the rob(14;22) using two distinct FISH approaches, i.e. LSP and WCP. LSP have been used in the majority of the previous sperm FISH studies of Robertsonian translocations. However, since the use of single LSP may be limited to sperm nuclei by the small size of fluorescent signals and the hybridization failure (Rousseaux et al., 1995), we chose to utilize contigs of BAC and PAC probes (Table I) to resolve the problem of probe efficiency and signal intensity. Because of their size, the WCP were easier to utilize and to detect on sperm nuclei. The use of WCP for human sperm screening was introduced by Rives et al. (1998), who demonstrated that WCP displayed both the specificity and the sensitivity required for in situ sperm scoring and required moderate in situ sperm decondensation to provide efficient labelling. The use of WCPs for sperm analysis of Robertsonian translocations was first reported by Morel et al. (2001) and recently by Rives et al. (2005) and Anahory et al. (2005). All these studies showed that WCPs were efficient for studying the meiotic segregation of Robertsonian translocations. However, contrary to Morel et al. (2001), we did not find that WCP allowed a systematic in situ distinction between normal and balanced spermatozoa. A significant proportion of sperm nuclei displayed partially overlapped WCP signals, which is in favour of sperm with the translocation.
The parallel use of LSP and WCP provided an internal control for the analysis of segregation pattern. In most experiments, both procedures gave similar results. However, significant variations between LSP and WCP findings were observed in the estimates of disomy rates. This observation might reflect the difficulties in standardizing and managing all the technical aspects of sperm FISH studies, such as the decondensation and the denaturation of sperm nuclei. Also, the weakness of the hybridization efficiency of LSP and the overlapping of signals might be significant limitative parameters in sperm preparations from translocation carriers (Rousseaux et al., 1995).
In the three carriers of the t(14;22), alternate segregation is largely dominant over adjacent segregations. This finding is consistent with results from previous sperm studies of common Robertsonian translocations t(13;14) and t(14;21), but also with data from the few rare Robertsonian translocations previously analysed. Just as for the t(13;14) (Luciani et al., 1984; Navarro et al., 1991) and the t(14;21) (Vidal et al., 1981), the pachytene analysis of the t(14;22) showed the predominant pairing of acrocentric trivalents in cis configuration which favours the alternate segregation of translocated chromosomes (MR Guichaoua, personal communication). Thus, in male meiosis, the behaviour of acrocentric chromosomes seems to be similar in all types of Robertsonian translocations, frequent and unfrequent, with a high predominance of alternate segregation.
In male carriers of Robertsonian translocations, significant variations in rates of imbalances have been reported. As observed in the present study and in previous segregation studies performed in carriers of the same Robertsonian translocation (Morel et al., 2001; Anton et al., 2004), a certain variability exists in the incidences of imbalances. This variability can be related to technical aspects of in situ hybridization and scoring but could also reflect variations in the formation and/or the meiotic behaviour of Robertsonian translocations. Indeed, studies on the molecular localization of breakpoints in Robertsonian translocations have revealed the high diversity of breakpoint locations, especially in unfrequent Robertsonian translocations (Page et al., 1996). This has suggested the existence of different mechanisms of formation for common and uncommon Robertsonian translocations (Page et al., 1996; Bandyopadhyay et al., 2002). We can speculate that variability in breakpoint location might result in discernible variations in the production of unbalanced gametes, even in cytogenetically identical Robertsonian translocations. Consequently, an important question is to know whether some specific Robertsonian translocations, in particular the rare ones, could be more prone to produce imbalances through meiosis. The mean incidence of imbalances observed in sperm from t(13;14) and t(14;21) carriers was 13.2 and 10.6%, respectively, whereas the mean imbalance rate in rare non-homologous rearrangements reached 15.9%. In particular, the three translocations t(14;22) analysed here displayed similar elevated incidences of unbalanced spermatozoa, around 19.5%. Chromosomes 14 and 22 are the acrocentric chromosomes displaying the most diversity in breakpoint locations when involved in Robertsonian translocations (Page et al., 1996). This could result in a higher propensity for producing imbalances through meiosis. Segregation analysis of new t(14;22) and other rare Robertsonian translocations are required to accurately investigate this question. It is also interesting to note that higher rates of disomies 14 and 22 over nullisomies were found in the three cases analysed. This is the opposite of what is found from several FISH studies on t(13;14) and t(14;21) where reduced incidences of disomy over nullisomy were reported (Honda et al., 2000; Morel et al., 2001; Anton et al., 2004). A similar higher rate of disomic sperm was observed by Frydman et al. (2001) in a carrier of a t(13;14). This finding may be interpreted as artefactual because of the possibility of unequal hybridization efficiency of probes (Rousseaux et al., 1995; Morel et al., 2001). Honda et al. (2000) and then Anton et al. (2004) have postulated a relation with meiotic checkpoint and maturation arrest to explain these differences in imbalance rates. In addition, the variability in breakpoints among translocations could affect the production of imbalances and explain the differences observed between the t(14;22) translocation and the common Robertsonian translocations.
Breakpoint diversity could also be one of the keys to the disturbances of sperm production. Spermatogenesis in male carriers of Robertsonian translocation is variably affected, ranging from normal to oligoasthenospermia or azoospermia. The three analysed carriers have different semen quality, involving normospermia, teratospermia and oligoasthenospermia, but all displayed similar rates of imbalances. These data support the hypothesis of Rousseaux et al. (1995) that spermatogenesis disruption and segregation patterns could be independent processes. It was postulated that the association between the trivalent and the XY body may impair spermatogenesis (Johannisson et al., 1993), by producing X-inactivation disturbances and subsequent germ cell deterioration. The deleterious associations of the trivalent and the XY body are exclusive of the free, non-synapsed short arms of the normal chromosomes (Solari, 1999). One can postulate that the presence and the length of free segments depend on the location of breakpoints in translocated chromosomes and consequently vary from one translocation to another, thus leading to the variable alterations of spermatogenesis observed in Robertsonian translocation carriers. Further studies combining sperm segregation analysis and molecular location of breakpoints are needed to study this question.
|
Acknowledgements |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionAcknowledgementsReferences |
|---|
This study was supported by a French research project PHRC (No. 7732) from the CHU of Montpellier.
We gratefully thank Professor Mariano Rocchi and Wellcome Trust Sanger Institute for providing the BAC and PAC clones used in this study.
|
References |
|---|
|
TopAbstractIntroductionMaterials and methodsResultsDiscussionAcknowledgementsReferences |
|---|
Acar H, Yildirim MS, Cora T and Ceylaner S (2002) Evaluation of segregation patterns of 21;21 Robertsonian translocation along with sex chromosomes and interchromosomal effects in sperm nuclei of carrier by FISH technique. Mol Reprod Dev 63,232–236.[CrossRef][Web of Science][Medline]
Anahory T, Hamamah S, Andreo B, Hédon B, Claustre M, Sarda P and Pellestor F (2005) Sperm segregation analysis of a (13;22) Robertsonian translocation carrier by FISH: a comparison of locus-specific probe and whole chromosome painting. Hum Reprod 20,1850–1854.
Anton E, Blanco J, Egozcue J and Vidal F (2004) Sperm FISH studies in seven male carriers of Robertsonian translocation t(13;14)(q10;q10). Hum Reprod 19,1345–1351.
Baccetti B, Capitani S, Collodel G, Estenoz M, Gambera L and Piomboni P (2002) Infertile spermatozoa in a human carrier of robertsonian translocation 14;22. Fertil Steril 78,1127–1130.[CrossRef][Web of Science][Medline]
Bandyopadhyay R, Heller A, Knox-DuBois C, McCaskill C, Berend SA, Page SL and Shaffer LG (2002) Parental origin and timing of de novo Robertsonian translocation formation. Am J Hum Genet 71,1456–1462.[CrossRef][Web of Science][Medline]
Boue A and Gallano P (1984) A collaborative study of the segregation of inherited chromosome structural rearrangements in 1356 prenatal diagnoses. Prenat Diagn 4,45–67.
Frydman N, Romana S, Le Lorc’h M, Vekemans M, Frydman R and Tachdjian G (2001) Assisting reproduction of infertile men carrying a Robertsonian translocation. Hum Reprod 16,2274–2277.
Gardner RJM and Sutherland GR (2004) Chromosome Abnormalities and Genetic Counselling, 3rd edn. Oxford University Press, Oxford, UK.
Guichaoua MR, Quack B, Speed RM, Noel B, Chandley AC and Luciani JM (1990) Infertility in human males with autosomal translocations: meiotic study of a 14;22 Robertsonian translocation. Hum Genet 86,162–166.[Web of Science][Medline]
Honda H, Miharu N, Samura O, He H and Ohama K (2000) Meiotic segregation analysis of a 14;21 Robertsonian translocation carrier by fluorescence in situ hybridization. Hum Genet 106,188–193.[CrossRef][Web of Science][Medline]
Johannisson R, Schwinger E, Wolff HH, vom Ende V and Lohrs U (1993) The effect of 13;14 Robertsonian translocations on germ-cell differentiation in infertile males. Cytogenet Cell Genet 63,151–155.[Web of Science][Medline]
Kotzot D and Utermann G (2005) Uniparental disomy (UPD) other than 15: phenotypes and bibliography updated. Am J Med Genet A 136,287–305.
Luciani JM, Guichaoua MR, Mattei A and Morazzani MR (1984) Pachyene analysis of a man with a 13q;14q translocation and infertility. Cytogenet Cell Genet 38,14–22.[Web of Science][Medline]
Martin RH, Ko E and Hildebrand K (1992) Analysis of sperm chromosome complements from a man heterozygous for a robertsonian translocation 45,XY,t(15q;22q). Am J Med Genet 43,855–857.[CrossRef][Web of Science][Medline]
Morel F, Roux C and Bresson JL (2001) FISH analysis of the chromosomal status of spermatozoa from three men with 45,XY,der(13;14)(q10;q10) karyotype. Mol Hum Reprod 7,483–488.
Morel F, Douet-Guilbert N, Le Bris MJ, Herry A, Amice V, Amice J and De Braekeleer M (2004) Meiotic segregation of translocations during male gametogenesis. Int J Androl 27,200–212.[CrossRef][Web of Science][Medline]
Navarro J, Vidal F, Benet J, Templado C and Marinas Egozcue J (1991) XY-trivalent association and synaptic anomalies in a male carrier of a Robertsonian t(13;14) translocation. Hum Reprod 6,376–381.
Page SL, Shin JC, Han JY, Choo KH and Shaffer LG (1996) Breakpoint diversity illustrates distinct mechanisms for Robertsonian translocation formation. Hum Mol Genet 5,1279–1288.
Pellestor F (1990) Analysis of meiotic segregation in a man heterozygous for a 13;15 Robertsonian translocation and a review of the literature. Hum Genet 85,49–54.[Web of Science][Medline]
Rives N, Mazurier S, Bellet D, Joly G and Mace B (1998) Assessment of autosome and gonosome disomy in human sperm nuclei by chromosome painting. Hum Genet 102,616–623.[CrossRef][Web of Science][Medline]
Rives N, Ravel C, Duchesne V, Siffroi JP, Mousset-Simeon N and Mace B (2005) Molecular cytogenetics analysis with whole chromosome paint probes of sperm nuclei from a (13;15) Robertsonian translocation carrier. J Hum Genet 50,360–364.[CrossRef][Web of Science][Medline]
Rousseaux S, Chevret E, Monteil M, Cozzi J, Pelletier R, Delafontaine D and Sele B (1995) Sperm nuclei analysis of a Robertsonian t(14q21q) carrier, by FISH, using three plasmids and two YAC probes. Hum Genet 96,655–660.[CrossRef][Web of Science][Medline]
Silverstein S, Lerer I, Sagi M, Frumkin A, Ben-Neriah Z and Abeliovich D (2002) Uniparental disomy in fetuses diagnosed with balanced Robertsonian translocations: risk estimate. Prenat Diagn 22,649–651.[CrossRef][Web of Science][Medline]
Solari AJ (1999) Synaptonemal complex analysis in human male infertility. Eur J Histochem 43,265–276.[Web of Science][Medline]
Spence JE, Perciaccante RG, Greig GM, Willard HF, Ledbetter DH, Hejtmancik JF, Pollack MS, O’Brien WE and Beaudet AL (1988) Uniparental disomy as a mechanism for human genetic disease. Am J Hum Genet 42,217–226.[Web of Science][Medline]
Sutton VR and Shaffer LG (2000) Search for imprinted regions on chromosome 14: comparison of maternal and paternal UPD cases with cases of chromosome 14 deletion. Am J Med Genet 93,381–387.
Syme RM and Martin RH (1992) Meiotic segregation of a 21;22 Robertsonian translocation. Hum Reprod 7,825–829.
Therman E, Susman B and Denniston C (1989) The nonrandom participation of human acrocentric chromosomes in Robertsonian translocations. Ann Hum Genet 53,49–65.[Web of Science][Medline]
Vidal F, Templado C, Navarro J, Marina S and Egozcue S (1981) Meiotic and synaptonemal complex studies in a 14–21 translocation carrier. Int J Androl 5,21–26.[Medline]
Submitted on October 25, 2005; resubmitted on December 1, 2005; accepted on December 6, 2005.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. Pinton, A. Calgaro, N. Bonnet, S. Ferchaud, S. Billoux, A.M. Dudez, N. Mary, K. Massip, A. Bonnet-Garnier, M. Yerle, et al. Influence of sex on the meiotic segregation of a t(13;17) Robertsonian translocation: a case study in the pig Hum. Reprod., August 1, 2009; 24(8): 2034 - 2043. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R.H. Martin Cytogenetic determinants of male fertility Hum. Reprod. Update, June 4, 2008; (2008) dmn017v1. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Anton, F. Vidal, and J. Blanco Role of sperm FISH studies in the genetic reproductive advice of structural reorganization carriers Hum. Reprod., August 1, 2007; 22(8): 2088 - 2092. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Perrin, N. Douet-Guilbert, B. Laudier, M.L. Couet, F. Guerif, D. Royere, M.J. Le Bris, M. De Braekeleer, and F. Morel Meiotic segregation in spermatozoa of a 45,XY,-14,der(18)t(14;18)(q11;p11.3) translocation carrier: A Case Report Hum. Reprod., March 1, 2007; 22(3): 729 - 732. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||