scholarly journals Meiotic Heterogeneity of Trivalent Structure and Interchromosomal Effect in Blastocysts With Robertsonian Translocations

2021 ◽  
Vol 12 ◽  
Author(s):  
Shuo Zhang ◽  
Caixia Lei ◽  
Junping Wu ◽  
Jing Zhou ◽  
Min Xiao ◽  
...  
Keyword(s):  
Robertsonian Translocation ◽  
Segregation Pattern ◽  
Inherited Disorders ◽  
Preimplantation Genetic Testing ◽  
Robertsonian Translocations ◽  
Reproductive Risk ◽  
Interchromosomal Effect ◽  
Additional Chromosome ◽  
Stratified Analysis ◽  
Mosaic Aneuploidy

BackgroundRobertsonian translocations are common structural rearrangements and confer an increased genetic reproductive risk due to the formation of trivalent structure during meiosis. Studies on trivalent structure show meiotic heterogeneity between different translocation carriers, although the factors causing heterogeneity have not been well elaborated in blastocysts. It is also not yet known whether interchromosomal effect (ICE) phenomenon occurs in comparison with suitable non-translocation control patients. Herein, we aimed to evaluate the factors that cause meiotic heterogeneity of trivalent structure and the ICE phenomenon.MethodsWe designed a retrospective study, comprising 217 Robertsonian translocation carriers and 134 patients with the risk of transmitting monogenic inherited disorders (RTMIDs) that underwent preimplantation genetic testing (PGT). Data was collected between March 2014 and December 2019. The segregation products of trivalent structure were analyzed based on the carrier’s gender, age and translocation type. In addition, to analyze ICE phenomenon, aneuploidy abnormalities of non-translocation chromosomes from Robertsonian translocation carriers were compared with those from patients with RTMIDs.ResultsWe found that the percentage of male carriers with alternate segregation pattern was significantly higher [P < 0.001, odds ratio (OR) = 2.95] than that in female carriers, while the percentage of adjacent segregation pattern was lower (P < 0.001, OR = 0.33). By contrast, no difference was observed between young and older carriers when performing stratified analysis by age. Furthermore, segregation pattern was associated with the D;G chromosomes involved in Robertsonian translocation: the rate of alternate segregation pattern in Rob(13;14) carriers was significantly higher (P = 0.010, OR = 1.74) than that in Rob(14;21) carriers, whereas the rate of adjacent segregation pattern was lower (P = 0.032, OR = 0.63). Moreover, the results revealed that the trivalent structure could significantly increase the frequencies of chromosome aneuploidies 1.30 times in Robertsonian translocation carriers compared with patients with RTMIDs (P = 0.026), especially for the male and young subgroups (P = 0.030, OR = 1.35 and P = 0.012, OR = 1.40), while the mosaic aneuploidy abnormalities presented no statistical difference.ConclusionsOur study demonstrated that meiotic segregation heterogeneity of trivalent structure is associated with the carrier’s gender and translocation type, and it is independent of carrier’s age. ICE phenomenon exists during meiosis and then increases the frequencies of additional chromosome abnormalities.

scholarly journals New Recommendations for Robertsonian Translocation Management After Preimplantation Genetic Testing of Structural Rearrangement (PGT-SR) Attempts: What Should Be Done With Mosaic Embryos?

2020 ◽  
Author(s):  
Reda Zenagui ◽  
Izabel Bernicot ◽  
Cendrine Ciabrini ◽  
Alice Ferrieres Hoa ◽  
Christel Castelli ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Robertsonian Translocation ◽  
Structural Rearrangement ◽  
Strategy Choice ◽  
Preimplantation Genetic Testing ◽  
Robertsonian Translocations ◽  
Increased Risk ◽  
Significant Difference ◽  
Mosaic Embryo ◽  
Repeated Miscarriages

Abstract Robertsonian translocation (RT) carriers are phenotypically normal, but they are known to be at increased risk of repeated miscarriages compared with the general population estimated at about 15% of pregnancies, and also resulting in the birth of a child with a mental retardation or congenital anomalies. Preimplantation Genetic Testing (PGT) is therefore a solution for RT carriers. An appropriate probe strategy allows to differentiate balanced embryos, unbalanced embryos, and mosaic embryos. We performed the first comparative analysis between two or three probes FISH strategies to analyze if a probe strategy choice for PGT-SR studies of Robertsonian translocations (RT) influences the fate of embryos? Our investigations present 13 years of experience of PGT for Robertsonian translocation carriers to improve the accuracy of abnormality detections. A deeper analysis of 283 PGT-SR attempts by comparing two strategies of probes highlighted the irrelevance of using a third probe for FISH diagnosis and above all a significant difference of mosaic embryo rates between probe strategies. These findings could be used as new recommendations of Robertsonian translocation management in many laboratories to improve their practices. It could be readily run, less expensive, reliable and accurate. Furthermore, the propounded strategy of mosaic embryo transfer should be considered after a detailed genetic counseling.

Analysis of Meiotic Segregation Pattern and Interchromosomal Effects in a Bull Heterozygous for a 3/16 Robertsonian Translocation

2018 ◽  
Vol 156 (4) ◽  
pp. 197-203 ◽  
Author(s):  
Harmonie Barasc ◽  
Nathalie Mouney-Bonnet ◽  
Clémence Peigney ◽  
Anne Calgaro ◽  
Clémence Revel ◽  
...  
Keyword(s):  
Robertsonian Translocation ◽  
Chromosomal Rearrangements ◽  
Segregation Pattern ◽  
Fish Analysis ◽  
Meiotic Segregation ◽  
Robertsonian Translocations ◽  
Sperm Nuclei ◽  
Meiotic Segregation Pattern ◽  
First Time ◽  
Low Rate

Robertsonian translocations are the most frequent chromosomal rearrangements detected in cattle. Here, we report on the detection of a new Robertsonian translocation between chromosomes BTA3 and BTA16. This rob(3;16) was dicentric, suggesting that its occurrence was recent. FISH analysis of decondensed sperm nuclei revealed a relatively low rate of unbalanced gametes produced by adjacent segregation (5.87%). In addition, and for the first time in bovines, a significant interchromosomal effect (ICE) was detected for 2 different autosomes: BTA17 (global disomy + nullisomy rate of 9%) and BTA20 (1.8%). These results suggest that ICE should be taken into consideration when assessing the putative effect of Robertsonian translocations on reproduction.

scholarly journals How much, if anything, do we know about sperm chromosomes of Robertsonian translocation carriers?

2020 ◽  
Vol 77 (23) ◽  
pp. 4765-4785
Author(s):  
Ewa Wiland ◽  
Marta Olszewska ◽  
Tomasz Woźniak ◽  
Maciej Kurpisz
Keyword(s):  
Robertsonian Translocation ◽  
Molecular Classification ◽  
Common Type ◽  
Destructive Effect ◽  
Robertsonian Translocations ◽  
Class 1 ◽  
The Common ◽  
Sperm Chromosomes

Abstract In men with oligozoospermia, Robertsonian translocations (RobTs) are the most common type of autosomal aberrations. The most commonly occurring types are rob(13;14) and rob(14;21), and other types of RobTs are described as ‘rare’ cases. Based on molecular research, all RobTs can be broadly classified into Class 1 and Class 2. Class 1 translocations produce the same breakpoints within their RobT type, but Class 2 translocations are predicted to form during meiosis or mitosis through a variety of mechanisms, resulting in variation in the breakpoint locations. This review seeks to analyse the available data addressing the question of whether the molecular classification of RobTs into Classes 1 and 2 and/or the type of DD/GG/DG symmetry of the involved chromosomes is reflected in the efficiency of spermatogenesis. The lowest frequency value calculated for the rate of alternate segregants was found for rob(13;15) carriers (Class 2, symmetry DD) and the highest for rob(13;21) carriers (Class 2, DG symmetry). The aneuploidy values for the rare RobT (Class 2) and common rob(14;21) (Class 1) groups together exhibited similarities while differing from those for the common rob(13;14) (Class 1) group. Considering the division of RobT carriers into those with normozoospermia and those with oligoasthenozoospermia, it was found that the number of carriers with elevated levels of aneuploidy was unexpectedly quite similar and high (approx. 70%) in the two subgroups. The reason(s) that the same RobT does not always show a similar destructive effect on fertility was also pointed out.

Preimplantation genetic testing of Robertsonian translocation by SNP array-based preimplantation genetic haplotyping

2018 ◽  
Vol 38 (8) ◽  
pp. 547-554 ◽  
Author(s):  
Jing Wang ◽  
Yanhong Zeng ◽  
Chenhui Ding ◽  
Bin Cai ◽  
Baomin Lu ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Robertsonian Translocation ◽  
Snp Array ◽  
Preimplantation Genetic Testing ◽  
Preimplantation Genetic Haplotyping

Reproductive Risk of the Silent Carrier of Robertsonian Translocation

2013 ◽  
Vol 67 (1) ◽  
pp. 56 ◽  
Author(s):  
Selim Kolgeci ◽  
Jehona Kolgeci ◽  
Mehmedali Azemi ◽  
Ruke Shala ◽  
Aferdita Daka ◽  
...  
Keyword(s):  
Robertsonian Translocation ◽  
Reproductive Risk

scholarly journals Analysis of meiotic segregation patterns and interchromosomal effects in sperm from 13 robertsonian translocations

2017 ◽  
Vol 20 (1) ◽  
pp. 43-50 ◽  
Author(s):  
B Wang ◽  
B Nie ◽  
D Tang ◽  
R Li ◽  
X Liu ◽  
...  
Keyword(s):  
Robertsonian Translocation ◽  
Sex Chromosome ◽  
Chromosome Rearrangement ◽  
Chromosome 18 ◽  
Robertsonian Translocations ◽  
Increased Risk ◽  
Male Patients ◽  
Male Carriers ◽  
Unusual Type

Abstract The frequency of the Robertonian (ROB) translocation in newborn babies is approximately one in 1000. Robertsonian translocation is an unusual type of chromosome rearrangement caused by two particular chromosomes joining together. The aim of the study was to analyze the segregation of the ROB translocations in 13 male carriers, and to verify a possible inter-chromosomal effect (ICE) of the ROB translocation on chromosomes 18, X, and Y. Thirteen male patients were included in the study. Multicolor fluorescent in situ hybridization (FISH) was used to analyze chromosomes 13, 14, 15, 21, 22, 18, X and Y in sperm. Among the heterozygous ROB translocation carriers, the frequency of normal/balanced spermatozoa resulting from alternate segregation varied between 70.4 and 85.2%. The frequency of unbalanced spermatozoa resulting from adjacent segregation varied between 14.8 and 29.6%. Increased frequencies of aneuploidy for a sex chromosome were found in 10 ROB translocation carriers (P2-P8, P10-P12). Increased frequencies of aneuploidy for chromosome 18 were found in10 ROB translocation carriers (P3-P9, P11-P13). In addition, increased frequencies of diploid were found in 11 ROB translocation carriers (P2-P9, P11-P13). Among the homozygous ROB translocation carriers, the rate of balanced spermatozoa was 99.7% and the frequency of unbalanced spermatozoa was 0.3%. However, the frequencies of aneuploidy for a sex chromosome and chromosome 18 were normal. Despite the high number of normal/balanced frequencies, there remained many unbalanced spermatozoa resulting from alternate segregation. The ROB translocation carriers may be at an increased risk for ICE. Robertsonian translocation homozygosity could be seen as a potential speciation in humans with 44 chromosomes.

scholarly journals A genetic method for measuring non-disjunction in mice with Robertsonian translocations

1975 ◽  
Vol 26 (3) ◽  
pp. 283-295 ◽  
Author(s):  
Mary F. Lyon ◽  
Hazel C. Ward ◽  
Gillian M. Simpson
Keyword(s):  
Environmental Factors ◽  
High Frequency ◽  
Maternal Age ◽  
Robertsonian Translocation ◽  
Marker Gene ◽  
Robertsonian Translocations ◽  
Factors Affecting ◽  
Genetic Method ◽  
Total Progeny ◽  
Good Agreement

SUMMARYA high frequency of chromosomal non-disjunction occurs spontaneously in mice heterozygous for some Robertsonian translocations. If animals heterozygous for the translocation and homozygous for different alleles of a marker gene are mated together a few young homozygous for the marker arise through non-disjunction, and their frequency can be used as a measure. This method has been used with the Robertsonian translocation Rb(9.19)163H and the marker ruby ru (chr. 19); Rb(4.6)-2Bnr with brown (b) and misty (m) (chr. 4); and Rb(9.14)6Bnr with hairless (hr) and piebald (s) (chr. 14) respectively. The frequencies of marked young were: Rb163 0/5260 ruru; Rb2 21/1997 mm bb; and Rb6 19/1702 hrhr ss, and the corresponding calculated non-disjunction frequencies in each arm of the translocation were Rb163, <5 %; Rb2, 15%; Rb6, 15%. These figures show reasonably good agreement with values obtained by other methods. A search for genetic or environmental factors affecting the frequency of marked young in Rb2 and Rb6 revealed that in Rb2 the frequency increased with maternal age, whereas in Rb6 the maternal age of the marked young was non-significantly below that of the total progeny. The reasons for this discrepancy are not clear.

scholarly journals The Incidence of Mosaicism for Individual Chromosome in Human Blastocysts Is Correlated With Chromosome Length

2021 ◽  
Vol 11 ◽  
Author(s):  
Tzu-Hsuan Chuang ◽  
Ya-Ping Chang ◽  
Meng-Ju Lee ◽  
Huai-Ling Wang ◽  
Hsing-Hua Lai ◽  
...  
Keyword(s):  
Small Sample Size ◽  
Chromosome Length ◽  
Small Sample ◽  
Individual Chromosome ◽  
Preimplantation Genetic Testing ◽  
Comprehensive Chromosome Screening ◽  
Mosaic Embryo ◽  
Group A ◽  
Group B ◽  
Mosaic Aneuploidy

Mosaicism, known as partial aneuploidies, mostly originates from mitotic errors during the post-zygotic stage; it consists of different cell lineages within a human embryo. The incidence of mosaicism has not been shown to correlate with maternal age, and its correlation with individual chromosome characteristics has not been well investigated. In this study, the results of preimplantation genetic testing for aneuploidy (PGT-A) derived from 4,036 blastocysts (930 IVF couples) were collected from 2015 to 2017. Via next-generation sequencing for comprehensive chromosome screening, embryo ploidy was identified as aneuploid, mosaic, and euploid. Total mosaicism was classified into two categories: “mosaic euploid/aneuploidy” (with mosaic aneuploidy between 20 and 80%) and “mosaic and aneuploidy” (a uniformly abnormal embryo superimposed with mosaic aneuploidies). Frequency of mosaicism was analyzed according to the function of chromosomal lengths, which divides involved chromosomes into three groups: group A (156–249 Mb), group B (102–145 Mb), and group C (51–90 Mb). The results show that the aneuploidy was more frequent in group C than in group A and group B (A: 23.7%, B: 35.1, 41.2%, p &lt; 0.0001), while the mosaicism was more frequent in group A and group B than in group C [(Mosaic euploid/aneuploid) A: 14.6%, B: 12.4%, C: 9.9%, p &lt; 0.0001; (mosaic and aneuploid) A: 21.3%, B: 22.9%, C: 18.9%, p &lt; 0.0001; (Total mosaicism) A: 35.9%, B: 35.3%, C: 28.8%, p &lt; 0.0001]. The significantly higher frequency of aneuploidy was on the shorter chromosome (&lt; 90 Mb), and that of mosaicism was on the longer chromosomes (&gt; 100 Mb). The length association did not reach significance in the patients with advanced age (≥ 36 years), and of the chromosome-specific mosaicism rate, the highest prevalence was on chromosome 14 (5.8%), 1 (5.7%), and 9 (5.6%). Although the length association was observed via group comparison, there may be affecting mechanisms other than chromosomes length. Eventually, twenty patients with mosaic embryo cryotransfers resulted in six live births. No significant correlation was observed between the transfer outcomes and chromosome length; however, the analysis was limited by small sample size.

scholarly journals Case Report: Identification of a de novo Missense Mutation in the F8 Gene, p.(Phe690Leu)/c.2070C > A, Causing Hemophilia A: A Case Report

2021 ◽  
Vol 11 ◽  
Author(s):  
Haiyan Bai ◽  
Xia Xue ◽  
Li Tian ◽  
Xi Tong Liu ◽  
Qian Li
Keyword(s):  
Case Report ◽  
Missense Mutation ◽  
Sanger Sequencing ◽  
Hemophilia A ◽  
De Novo ◽  
Pathogenic Mutation ◽  
Site Amplification ◽  
Monogenic Disease ◽  
Inherited Disorders ◽  
Preimplantation Genetic Testing

Hemophilia A is an X-linked recessive bleeding disorder caused by various types of pathological defects in the factor VIII gene (F8/FVIII). Preimplantation genetic testing for monogenic disease (PGT-M) is a powerful tool to tackle the transmission of monogenic inherited disorders from generation to generation. In our case, a mutation in F8 had passed through female carriers in a hemophilia A family and resulted in two male patients with hemophilia A. To identify the etiological genetic variants of F8, next-generation sequencing (NGS) was used for chromosome copy number variation detection, Sanger sequencing to verify mutation sites, single nucleotide polymorphism (SNP) for site amplification, and sequencing to validate the genetic linkage. Finally, a novel missense mutation, p. (Phe690Leu)/c.2070C &gt; A, occurring in exon 13 of F8, was screened out as a pathogenic mutation. Following this, an F8 normal euploid blastocyst was transferred. At the 18th week, the pregnant mother underwent amniocentesis, NGS, Sanger sequencing, and SNP typing that further confirmed that the fetus had a healthy genotype. After delivery, a neonatal blood sample was sent for FVIII concentration detection, and the result established that the FVIII protein was rescued to a nearly average level. We first identified a new type of pathogenic mutation in F8, which has not been previously reported, selected a genetically healthy progeny for an affected family, and provided valuable knowledge of the diagnosis and treatment of hemophilia A.

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