Shuo Zhang1,2, Caixia Lei1, Junping Wu1, Haiyan Sun1, Jing Zhou1, Saijuan Zhu1, Jialong Wu1, Jing Fu1, Yijuan Sun1, Daru Lu2, Xiaoxi Sun1,3, Yueping Zhang1. 1. Shanghai Ji Ai Genetics & IVF Institute, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China. 2. State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Science, Fudan University, Shanghai 200438, China. 3. Key Laboratory of Female Reproductive Endocrine Related Diseases, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China.
Abstract
STUDY QUESTION: Do specific factors affect the segregation patterns of a quadrivalent structure and can the quadrivalent affect genome stability during meiosis? SUMMARY ANSWER: Meiotic segregation patterns can be affected by the carrier's gender and age, location of breakpoints and chromosome type, and the quadrivalent structure can increase genome instability during meiosis. WHAT IS KNOWN ALREADY: Carriers of reciprocal translocations have an increased genetic reproductive risk owing to the complex segregation patterns of a quadrivalent structure. However, the results of previous studies on the factors that affect segregation patterns seem to be contradictory, and the effect of a quadrivalent on genome stability during meiosis is unknown. STUDY DESIGN, SIZE, DURATION: We designed a retrospective study to analyze the segregation patterns of 24 chromosomes from reciprocal translocation and non-translocation patients. Data for 356 reciprocal translocation carriers and 53 patients with the risk to transmit monogenic inherited disorders (RTMIDs) undergoing PGD-single nucleotide polymorphism array analysis were collected. The study was performed between March 2014 and July 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: Segregation patterns of a quadrivalent in 1842 blastocysts from 466 assisted reproduction cycles of reciprocal translocation carriers were analyzed according to the location of chromosome breakpoints, the carrier's gender and age, and chromosome type. In addition, to analyze the effect of quadrivalent structure on genome stability, segregation products of chromosomes which are not involved in the translocation from translocation carriers were compared with those of 23 pairs of chromosomes in 318 blastocysts from 72 assisted reproduction cycles of patients with RTMIDs. MAIN RESULTS AND THE ROLE OF CHANCE: The percentage of adjacent-2 products with severe asymmetric quadrivalent was significantly higher than those with mild asymmetric quadrivalent (P = 0.020) while, in contrast, the incidence of 4:0/others was lower (P = 0.030). The frequencies of adjacent-1, adjacent-2 and 3:1 products differed between male and female carriers (P < 0.001, P = 0.015 and P = 0.001, respectively), and also for adjacent-1 and 4:0/others products in young versus older carriers (P = 0.04 and P = 0.002, respectively). In addition, adjacent-1 products of a quadrivalent with an acrocentric chromosome were significantly higher than those of a quadrivalent without an acrocentric chromosome (P = 0.001). Moreover, a quadrivalent could significantly increase the frequencies of abnormal chromosomes compared to patients with RTMIDs (P = 0.048, odds ratio (OR) = 1.43, 95% CI = 1.01-2.43), especially for the male carriers (P = 0.018, OR = 1.58, 95% CI = 1.08-2.25). In contrast, for older carriers, no difference was found in both aneuploidy and segmental anomalies compared to patients with RTMIDs. LIMITATIONS, REASONS FOR CAUTION: The study contained appropriate controls, yet the analysis was limited by a small number of control patients and embryos. WIDER IMPLICATIONS OF THE FINDINGS: Until now, there had been no definite report about the effect of quadrivalents on genome stability in reciprocal translocation carriers compared with control samples, and in the present study the large sample size ensured a detailed analysis of factors with a possible impact on segregation patterns. These data provide a better insight into the meiotic mechanisms involved in non-disjunction events in gametes from reciprocal translocation carriers. In addition, our results will help to provide each reciprocal translocation carrier couple undergoing PGD with more appropriate genetic counseling and a better understanding of the large numbers of abnormal embryos with chromosome aneuploidy. STUDY FUNDING/COMPETING INTEREST(S): The research was supported by the Research Funding of Shanghai Ji Ai Genetics & IVF Institute and the authors declare a lack of competing interests in this study.
STUDY QUESTION: Do specific factors affect the segregation patterns of a quadrivalent structure and can the quadrivalent affect genome stability during meiosis? SUMMARY ANSWER: Meiotic segregation patterns can be affected by the carrier's gender and age, location of breakpoints and chromosome type, and the quadrivalent structure can increase genome instability during meiosis. WHAT IS KNOWN ALREADY: Carriers of reciprocal translocations have an increased genetic reproductive risk owing to the complex segregation patterns of a quadrivalent structure. However, the results of previous studies on the factors that affect segregation patterns seem to be contradictory, and the effect of a quadrivalent on genome stability during meiosis is unknown. STUDY DESIGN, SIZE, DURATION: We designed a retrospective study to analyze the segregation patterns of 24 chromosomes from reciprocal translocation and non-translocation patients. Data for 356 reciprocal translocation carriers and 53 patients with the risk to transmit monogenic inherited disorders (RTMIDs) undergoing PGD-single nucleotide polymorphism array analysis were collected. The study was performed between March 2014 and July 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: Segregation patterns of a quadrivalent in 1842 blastocysts from 466 assisted reproduction cycles of reciprocal translocation carriers were analyzed according to the location of chromosome breakpoints, the carrier's gender and age, and chromosome type. In addition, to analyze the effect of quadrivalent structure on genome stability, segregation products of chromosomes which are not involved in the translocation from translocation carriers were compared with those of 23 pairs of chromosomes in 318 blastocysts from 72 assisted reproduction cycles of patients with RTMIDs. MAIN RESULTS AND THE ROLE OF CHANCE: The percentage of adjacent-2 products with severe asymmetric quadrivalent was significantly higher than those with mild asymmetric quadrivalent (P = 0.020) while, in contrast, the incidence of 4:0/others was lower (P = 0.030). The frequencies of adjacent-1, adjacent-2 and 3:1 products differed between male and female carriers (P < 0.001, P = 0.015 and P = 0.001, respectively), and also for adjacent-1 and 4:0/others products in young versus older carriers (P = 0.04 and P = 0.002, respectively). In addition, adjacent-1 products of a quadrivalent with an acrocentric chromosome were significantly higher than those of a quadrivalent without an acrocentric chromosome (P = 0.001). Moreover, a quadrivalent could significantly increase the frequencies of abnormal chromosomes compared to patients with RTMIDs (P = 0.048, odds ratio (OR) = 1.43, 95% CI = 1.01-2.43), especially for the male carriers (P = 0.018, OR = 1.58, 95% CI = 1.08-2.25). In contrast, for older carriers, no difference was found in both aneuploidy and segmental anomalies compared to patients with RTMIDs. LIMITATIONS, REASONS FOR CAUTION: The study contained appropriate controls, yet the analysis was limited by a small number of control patients and embryos. WIDER IMPLICATIONS OF THE FINDINGS: Until now, there had been no definite report about the effect of quadrivalents on genome stability in reciprocal translocation carriers compared with control samples, and in the present study the large sample size ensured a detailed analysis of factors with a possible impact on segregation patterns. These data provide a better insight into the meiotic mechanisms involved in non-disjunction events in gametes from reciprocal translocation carriers. In addition, our results will help to provide each reciprocal translocation carrier couple undergoing PGD with more appropriate genetic counseling and a better understanding of the large numbers of abnormal embryos with chromosome aneuploidy. STUDY FUNDING/COMPETING INTEREST(S): The research was supported by the Research Funding of Shanghai Ji Ai Genetics & IVF Institute and the authors declare a lack of competing interests in this study.
Authors: E Mateu-Brull; L Rodrigo; V Peinado; A Mercader; I Campos-Galindo; F Bronet; S García-Herrero; M Florensa; M Milán; C Rubio Journal: J Assist Reprod Genet Date: 2019-11-06 Impact factor: 3.412
Authors: Olga Tšuiko; Tuuli Dmitrijeva; Katrin Kask; Pille Tammur; Neeme Tõnisson; Andres Salumets; Tatjana Jatsenko Journal: Mol Cytogenet Date: 2019-06-18 Impact factor: 2.009