scholarly journals Distinguishing between carrier and noncarrier embryos with the use of long-read sequencing in preimplantation genetic testing for reciprocal translocations

Genomics ◽  
2020 ◽  
Vol 112 (1) ◽  
pp. 494-500 ◽  
Author(s):  
Judy F.C. Chow ◽  
Heidi H.Y. Cheng ◽  
Estella Y.L. Lau ◽  
William S.B. Yeung ◽  
Ernest H.Y. Ng
Keyword(s):  
Genetic Testing ◽  
Preimplantation Genetic Testing ◽  
Reciprocal Translocations ◽  
Long Read

scholarly journals Successful Birth After Preimplantation Genetic Testing for a Couple With Two Different Reciprocal Translocations and Review of the Literature

2020 ◽  
Author(s):  
Dun Liu ◽  
Chuangqi Chen ◽  
Xiqian Zhang ◽  
Mei Dong ◽  
Tianwen He ◽  
...  
Keyword(s):  
Genetic Counseling ◽  
Genetic Testing ◽  
Reciprocal Translocation ◽  
Carrier Status ◽  
Review Of The Literature ◽  
Preimplantation Genetic Testing ◽  
Reciprocal Translocations ◽  
Translocation Breakpoints ◽  
Next Generation Sequencing Ngs ◽  
Low Coverage

Abstract Background: Preimplantation genetic testing for chromosomal structural rearrangements (PGT-SR) is widely applied in couples with single reciprocal translocation to increase the chance for a healthy live birth. However, limited knowledge is known on the data of PGT-SR when both parents have a reciprocal translocation. Here, we for the first time present a rare instance of PGT-SR for a non-consanguineous couple in which both parents carried an independent balanced reciprocal translocation and show how relevant genetic counseling data can be generated.Methods: The precise translocation breakpoints were identified by whole genome low-coverage sequencing (WGLCS) and Sanger sequencing. Next-generation sequencing (NGS) combining with breakpoint-specific polymerase chain reaction (PCR) was used to define 24-chromosome and the carrier status of the euploid embryos.Results: Surprisingly, 66.7% day-5 blastocysts were found to be balanced for maternal reciprocal translocation while being normal for paternal translocation and thus transferable. The transferable embryo rate was significantly higher than that which would be expected theoretically. Transfer of one balanced embryo resulted in the birth of a healthy boy. Conclusion(s): Our data of PGT-SR together with a systematic review of the literature should help in providing couples carrying two different reciprocal translocations undergoing PGT-SR with more appropriate genetic counseling.

scholarly journals A Rapid NGS-Based Preimplantation Genetic Testing for Chromosomal Abnormalities in Day-3 Blastomere Biopsy Allows Embryo Transfer Within the Same Treatment Cycle

2021 ◽  
Vol 12 ◽  
Author(s):  
Yinghui Ye ◽  
Jieliang Ma ◽  
Long Cui ◽  
Sijia Lu ◽  
Fan Jin
Keyword(s):  
Genetic Testing ◽  
Embryo Transfer ◽  
Live Birth ◽  
De Novo ◽  
Clinical Pregnancy ◽  
Preimplantation Genetic Testing ◽  
Reciprocal Translocations ◽  
Robertsonian Translocations ◽  
Implantation Rates ◽  
Day 3 Embryos

Nowadays, most of the preimplantation genetic testing (PGT) is performed with a strategy of comprehensive chromosome screening and trophectoderm biopsy. Nevertheless, patients with ovarian insufficiency may not have competent blastocysts. In the present study, we aimed to establish the value of multiple annealing and looping-based amplification cycle (MALBAC)-based next-generation sequencing (NGS) for PGT in day-3 embryos. A total of 94.3% (1168/1239) of embryos yielded informative results, and the overall embryo euploid rate was 21.9% (256/1168). Overall, 225 embryos were transferred in 169 cycles with a clinical pregnancy rate of 49.1% (83/169). The live birth and implantation rates were 47.3% (80/169) and 44.4% (100/225), respectively. Double embryos transfer showed higher clinical pregnancy and live birth rates compared with single embryo transfer, but the implantation rates were similar (44.2% vs. 44.6%, P > 0.05). The euploid rate for reciprocal translocations (16.1%) was significantly lower than that for Robertsonian translocations (28.0%, P < 0.01) and inversions (28.0%, P < 0.01). However, higher percentages of embryos with de novo abnormalities were observed with Robertsonian translocations (23.3%, P < 0.01) and inversions (30.5%, P < 0.01) than with reciprocal translocations (11.6%). We demonstrated that NGS for PGT on day-3 embryos is an effective clinical application, particularly for patients with a diminished ovarian reserve and limited embryos.

scholarly journals De novo balanced reciprocal translocation mosaic t(1;3)(q42;q25) detected by prenatal genetic diagnosis: a fetus conceived using preimplantation genetic testing due to a t(12;14)(q22;q13) balanced paternal reciprocal translocation

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Shaoqin Zhang ◽  
Jianjiang Zhu ◽  
Hong Qi ◽  
Limei Xu ◽  
Lirong Cai ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Reciprocal Translocation ◽  
De Novo ◽  
Psychomotor Development ◽  
Chromosomal Microarray Analysis ◽  
Driving Mechanism ◽  
Balanced Translocation ◽  
Translocation Carrier ◽  
Preimplantation Genetic Testing ◽  
Reciprocal Translocations

Abstract Introduction De novo balanced reciprocal translocations mosaicism in fetus conceived using preimplantation genetic testing from a different balanced translocation carrier parent has been rarely reported. Methods Chromosomal microarray analysis, karyotype analysis and fluorescent in situ hybridization were performed to verify the type and heredity of the rearrangement. STR analysis was conducted to identify potential contamination and verify kinship. In addition, a local BLAST engine was performed to locate potentially homologous segments which might contribute to the translocation in breakpoints of chromosome. Results A rare de novo balanced reciprocal translocations mosaicism mos 46,XY,t(1;3)(q42;q25)[40]/46,XY[39] was diagnosed in a fetus conceived using preimplantation genetic testing due to a 46,XY,t(12;14)(q22;q13) balanced translocation carrier father through multiplatform genetic techniques. Two of the largest continuous high homology segments were identified in chromosomal band 1q42.12 and 3q25.2. At the 21-months follow up, infant has achieved all psychomotor development milestones as well as growth within the normal reference range. Conclusion We present a prenatal diagnosis of a rare de novo balanced reciprocal translocations mosaicism in a fetus who conceived by preimplantation genetic testing. The most reasonable driving mechanism was that a de novo mitotic error caused by nonallelic homologous recombination between 1q42.12 and 3q25.2 in a zygote within the first or early cell divisions, which results in a mosaic embryo with the variant present in a half proportion of cells.

scholarly journals Successful birth after preimplantation genetic testing for a couple with two different reciprocal translocations and review of the literature

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Dun Liu ◽  
Chuangqi Chen ◽  
Xiqian Zhang ◽  
Mei Dong ◽  
Tianwen He ◽  
...  
Keyword(s):  
Genetic Counseling ◽  
Genetic Testing ◽  
Reciprocal Translocation ◽  
Carrier Status ◽  
Review Of The Literature ◽  
Preimplantation Genetic Testing ◽  
Reciprocal Translocations ◽  
Translocation Breakpoints ◽  
Next Generation Sequencing Ngs ◽  
Low Coverage

Abstract Background Preimplantation genetic testing for chromosomal structural rearrangements (PGT-SR) is widely applied in couples with single reciprocal translocation to increase the chance for a healthy live birth. However, limited knowledge is known on the data of PGT-SR when both parents have a reciprocal translocation. Here, we for the first time present a rare instance of PGT-SR for a non-consanguineous couple in which both parents carried an independent balanced reciprocal translocation and show how relevant genetic counseling data can be generated. Methods The precise translocation breakpoints were identified by whole genome low-coverage sequencing (WGLCS) and Sanger sequencing. Next-generation sequencing (NGS) combining with breakpoint-specific polymerase chain reaction (PCR) was used to define 24-chromosome and the carrier status of the euploid embryos. Results Surprisingly, 2 out of 3 day-5 blastocysts were found to be balanced for maternal reciprocal translocation while being normal for paternal translocation and thus transferable. The transferable embryo rate was significantly higher than that which would be expected theoretically. Transfer of one balanced embryo resulted in the birth of a healthy boy. Conclusion(s) Our data of PGT-SR together with a systematic review of the literature should help in providing couples carrying two different reciprocal translocations undergoing PGT-SR with more appropriate genetic counseling.

scholarly journals Long-read sequencing and haplotype linkage analysis enabled preimplantation genetic testing for patients carrying pathogenic inversions

2019 ◽  
Vol 56 (11) ◽  
pp. 741-749 ◽  
Author(s):  
Shuo Zhang ◽  
Fan Liang ◽  
Caixia Lei ◽  
Junping Wu ◽  
Jing Fu ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Linkage Analysis ◽  
Sanger Sequencing ◽  
Normal Karyotype ◽  
Break Point ◽  
Molecular Techniques ◽  
Preimplantation Genetic Testing ◽  
Oxford Nanopore ◽  
Long Read ◽  
Break Points

BackgroundPreimplantation genetic testing (PGT) has already been applied in patients known to carry chromosomal structural variants to improve the clinical outcome of assisted reproduction. However, conventional molecular techniques are not capable of reliably distinguishing embryos that carry balanced inversion from those with a normal karyotype. We aim to evaluate the use of long-read sequencing in combination with haplotype linkage analysis to address this challenge.MethodsLong-read sequencing on Oxford Nanopore platform was employed to identify the precise positions of inversion break points in four patients. Comprehensive chromosomal screening and genome-wide haplotype linkage analysis were performed based on SNP microarray. The haplotypes, including the break point regions, the whole chromosomes involved in the inversion and the corresponding homologous chromosomes, were established using informative SNPs.ResultsAll the inversion break points were successfully identified by long-read sequencing and validated by Sanger sequencing, and on average only 13 bp differences were observed between break points inferred by long-read sequencing and Sanger sequencing. Eighteen blastocysts were biopsied and tested, in which 10 were aneuploid or unbalanced and eight were diploid with normal or balanced inversion karyotypes. Diploid embryos were transferred back to patients, the predictive results of the current methodology were consistent with fetal karyotypes of amniotic fluid or cord blood.ConclusionsNanopore long-read sequencing is a powerful method to assay chromosomal inversions and identify exact break points. Identification of inversion break points combined with haplotype linkage analysis is an efficient strategy to distinguish embryos with normal or balanced inversion karyotypes, facilitating PGT applications.

scholarly journals Analysis of the embryos genetic characteristics and methodologies of human translocations research

2020 ◽  
Vol 27 ◽  
pp. 190-195
Author(s):  
O. Y. Verlinsky ◽  
J. V. Gontar ◽  
N. I. Kazachkova ◽  
Y. V. Laxhno ◽  
I. E. Ilyin ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Chromosome Structure ◽  
Structural Rearrangements ◽  
Reproductive Disorders ◽  
Preimplantation Genetic Testing ◽  
Reciprocal Translocations ◽  
Genetic Characteristics ◽  
Mothers And Fathers ◽  
Trophectoderm Cells ◽  
Classical Cytogenetics

Aim. Assessment of the embryos genetic characteristics from translocation carriers and analysis of the translocation research methodology. Methods. The chromosome structure was analyzed using classical cytogenetics methods, GTG, FISH. Preimplantation genetic testing to identify structural rearrangements of the embryos chromosomes was performed on trophectoderm cells using NGS and FISH methods. Results. The proportion of translocation carriers in the sample of patients with reproductive disorders (n = 6156) was 1.1 %, with 0.4 % – for Robertson translations and 0.8 % for reciprocal ones. 5-day-old embryos with balanced reciprocal translocations are 3-4 times less than with unbalanced ones. Euploid embryos with balanced variants from translocation carriers-mothers and -fathers, amounted to 14.3 % and 12.5 %. Aneuploid embryos with unbalanced translocations accounted for 59.2 % of mothers and 63.2 % of fathers of all received embryos, 80.6 % and 77.8 % of unbalanced ones. Conclusions. Understanding the prevalence of segmental karyotype disorders among the population and modern research methods allows to optimize reproductive care for patients. Keywords: reciprocal translocations, embryos, PGT-SR, NGS, FISH.

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