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Novel PGD strategy based on single sperm linkage analysis for carriers of single gene pathogenic variant and chromosome reciprocal translocation

  • Genetics
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

Preimplantation genetic diagnosis (PGD) analysis can be challenging for couples who carry more than one genetic condition. In this study, we describe a new PGD strategy to select which embryo(s) to transfer for two clinically challenging cases. Both cases lack essential family members for linkage analysis including de novo mutation combined with reciprocal translocation.

Methods

Diverging from conventional method, we performed direct point mutation detection, quantitative analysis of gene copy number, combined with linkage analysis assisted by SNP information from single sperm (or polar bodies), thus establishing an all-in-one protocol for single embryonic cell preimplantation diagnosis for two co-existing genetic conditions (monogenic disease and chromosomal abnormality) on the NGS-based platform.

Results

Using this newly developed method, 15 embryos from two cases were screened, and two embryos were determined as free of the monogenic disease and specific chromosomal abnormalities created by the prospective father’s reciprocal translocations.

Conclusion

This novel PGD strategy could effectively select unaffected embryo(s) for couples affected with or carrying a monogenetic disease and a reciprocal chromosome translocation concurrently.

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Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, Beijing, 100191, China

    Yuqian Wang, Xiaohui Zhu, Zhiqiang Yan, Xu Zhi, Shuo Guan, Ying Kuo, Yanli Nie, Ying Lian, Jin Huang, Yuan Wei, Ping Liu, Rong Li, Jie Qiao & Liying Yan

  2. Key Laboratory of Assisted Reproduction, Ministry of Education and Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, 100191, China

    Yuqian Wang, Xiaohui Zhu, Zhiqiang Yan, Xu Zhi, Shuo Guan, Ying Kuo, Yanli Nie, Ying Lian, Jin Huang, Yuan Wei, Ping Liu, Rong Li, Jie Qiao & Liying Yan

  3. Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, 100871, China

    Zhiqiang Yan & Jie Qiao

  4. Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China

    Zhiqiang Yan & Jie Qiao

  5. Beijing Advanced Innovation Center for Genomics, Peking University, Beijing, 100191, China

    Jie Qiao

Authors
  1. Yuqian Wang
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  2. Xiaohui Zhu
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  14. Liying Yan
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Correspondence to Liying Yan.

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Yuqian Wang and Xiaohui Zhu are joint First Authors

Electronic supplementary material

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ESM 2

Fig. S1 Inherited patterns of chromosome 5 and identification of SMN1 and SMN2 copy numbers. A: MLPA results of SMN1 and SMN2 copy numbers. (0.8): detection value. We deduce the husband carried 1 copy SMN2 Exon7, and there is an allowable error between actual copy number and detection copy number. B: Inherited patterns of Chr 5 in this family. Inherited patterns are based on the SMN1 gene and ignore chromosome exchange. Nor: normal chromosome around breakpoint; der: derivative chromosome around breakpoint. C: Inherited patterns of Chr 5 in six embryos. We illustrated chromosome exchanges that influenced the diagnosis of SMN1, like E2, and omitted irrelevant exchanges for clarity (TIF 4.21 mb)

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Wang, Y., Zhu, X., Yan, Z. et al. Novel PGD strategy based on single sperm linkage analysis for carriers of single gene pathogenic variant and chromosome reciprocal translocation. J Assist Reprod Genet 37, 1239–1250 (2020). https://doi.org/10.1007/s10815-020-01753-2

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  • DOI: https://doi.org/10.1007/s10815-020-01753-2

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