A comprehensive and universal approach for embryo testing in patients with different genetic disorders
Abstract Background In vitro fertilization (IVF) with preimplantation genetic testing (PGT) has markedly improved clinical pregnancy outcomes for carriers of gene mutations or chromosomal structural rearrangements by the selection of embryos free of disease‐causing genes and chromosome abnormalities...
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| Format: | Article |
| Language: | English |
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Wiley
2021-07-01
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| Series: | Clinical and Translational Medicine |
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| Online Access: | https://doi.org/10.1002/ctm2.490 |
| _version_ | 1811323159255711744 |
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| author | Shuo Zhang Caixia Lei Junping Wu Min Xiao Jing Zhou Saijuan Zhu Jing Fu Daru Lu Xiaoxi Sun Congjian Xu |
| author_facet | Shuo Zhang Caixia Lei Junping Wu Min Xiao Jing Zhou Saijuan Zhu Jing Fu Daru Lu Xiaoxi Sun Congjian Xu |
| author_sort | Shuo Zhang |
| collection | DOAJ |
| description | Abstract Background In vitro fertilization (IVF) with preimplantation genetic testing (PGT) has markedly improved clinical pregnancy outcomes for carriers of gene mutations or chromosomal structural rearrangements by the selection of embryos free of disease‐causing genes and chromosome abnormalities. However, for detecting whole or segmental chromosome aneuploidies, gene variants or balanced chromosome rearrangements in the same embryo require separate procedures, and none of the existing detection platforms is universal for all patients with different genetic disorders. Methods Here, we report a cost‐effective, family‐based haplotype phasing approach that can simultaneously evaluate multiple genetic variants, including monogenic disorders, aneuploidy, and balanced chromosome rearrangements in the same embryo with a single test. A total of 12 monogenic diseases carrier couples and either of them carried chromosomal rearrangements were enrolled simultaneously in this present study. Genome‐wide genotyping was performed with single‐nucleotide polymorphism (SNP)‐array, and aneuploidies were analyzed through SNP allele frequency and Log R ratio. Parental haplotypes were phased by an available genotype from a close relative, and the embryonic genome‐wide haplotypes were determined through family haplotype linkage analysis (FHLA). Disease‐causing genes and chromosomal rearrangements were detected by haplotypes located within the 2 Mb region covering the targeted genes or breakpoint regions. Results Twelve blastocysts were thawed, and then transferred into the uterus of female patients. Nine pregnancies had reached the second trimester and five healthy babies have been born. Fetus validation results, performed with the amniotic fluid or umbilical cord blood samples, were consistent with those at the blastocyst stage diagnosed by PGT. Conclusions We demonstrate that SNP‐based FHLA enables the accurate genetic detection of a wide spectrum of monogenic diseases and chromosome abnormalities in embryos, preventing the transfer of parental genetic abnormalities to the fetus. This method can be implemented as a universal platform for embryo testing in patients with different genetic disorders. |
| first_indexed | 2024-04-13T13:50:09Z |
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| id | doaj.art-875d99813923473b9a5e35da8bc5f499 |
| institution | Directory Open Access Journal |
| issn | 2001-1326 |
| language | English |
| last_indexed | 2024-04-13T13:50:09Z |
| publishDate | 2021-07-01 |
| publisher | Wiley |
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| series | Clinical and Translational Medicine |
| spelling | doaj.art-875d99813923473b9a5e35da8bc5f4992022-12-22T02:44:22ZengWileyClinical and Translational Medicine2001-13262021-07-01117n/an/a10.1002/ctm2.490A comprehensive and universal approach for embryo testing in patients with different genetic disordersShuo Zhang0Caixia Lei1Junping Wu2Min Xiao3Jing Zhou4Saijuan Zhu5Jing Fu6Daru Lu7Xiaoxi Sun8Congjian Xu9Shanghai Ji Ai Genetics & IVF Institute, Obstetrics and Gynecology Hospital Fudan University Shanghai ChinaShanghai Ji Ai Genetics & IVF Institute, Obstetrics and Gynecology Hospital Fudan University Shanghai ChinaShanghai Ji Ai Genetics & IVF Institute, Obstetrics and Gynecology Hospital Fudan University Shanghai ChinaShanghai Ji Ai Genetics & IVF Institute, Obstetrics and Gynecology Hospital Fudan University Shanghai ChinaShanghai Ji Ai Genetics & IVF Institute, Obstetrics and Gynecology Hospital Fudan University Shanghai ChinaShanghai Ji Ai Genetics & IVF Institute, Obstetrics and Gynecology Hospital Fudan University Shanghai ChinaShanghai Ji Ai Genetics & IVF Institute, Obstetrics and Gynecology Hospital Fudan University Shanghai ChinaState Key Laboratory of Genetic Engineering, School of Life Science Fudan University Shanghai ChinaShanghai Ji Ai Genetics & IVF Institute, Obstetrics and Gynecology Hospital Fudan University Shanghai ChinaShanghai Ji Ai Genetics & IVF Institute, Obstetrics and Gynecology Hospital Fudan University Shanghai ChinaAbstract Background In vitro fertilization (IVF) with preimplantation genetic testing (PGT) has markedly improved clinical pregnancy outcomes for carriers of gene mutations or chromosomal structural rearrangements by the selection of embryos free of disease‐causing genes and chromosome abnormalities. However, for detecting whole or segmental chromosome aneuploidies, gene variants or balanced chromosome rearrangements in the same embryo require separate procedures, and none of the existing detection platforms is universal for all patients with different genetic disorders. Methods Here, we report a cost‐effective, family‐based haplotype phasing approach that can simultaneously evaluate multiple genetic variants, including monogenic disorders, aneuploidy, and balanced chromosome rearrangements in the same embryo with a single test. A total of 12 monogenic diseases carrier couples and either of them carried chromosomal rearrangements were enrolled simultaneously in this present study. Genome‐wide genotyping was performed with single‐nucleotide polymorphism (SNP)‐array, and aneuploidies were analyzed through SNP allele frequency and Log R ratio. Parental haplotypes were phased by an available genotype from a close relative, and the embryonic genome‐wide haplotypes were determined through family haplotype linkage analysis (FHLA). Disease‐causing genes and chromosomal rearrangements were detected by haplotypes located within the 2 Mb region covering the targeted genes or breakpoint regions. Results Twelve blastocysts were thawed, and then transferred into the uterus of female patients. Nine pregnancies had reached the second trimester and five healthy babies have been born. Fetus validation results, performed with the amniotic fluid or umbilical cord blood samples, were consistent with those at the blastocyst stage diagnosed by PGT. Conclusions We demonstrate that SNP‐based FHLA enables the accurate genetic detection of a wide spectrum of monogenic diseases and chromosome abnormalities in embryos, preventing the transfer of parental genetic abnormalities to the fetus. This method can be implemented as a universal platform for embryo testing in patients with different genetic disorders.https://doi.org/10.1002/ctm2.490chromosomal rearrangementschromosome aneuploidiesfamily haplotype linkage analysismonogenic diseasespreimplantation genetic testing |
| spellingShingle | Shuo Zhang Caixia Lei Junping Wu Min Xiao Jing Zhou Saijuan Zhu Jing Fu Daru Lu Xiaoxi Sun Congjian Xu A comprehensive and universal approach for embryo testing in patients with different genetic disorders Clinical and Translational Medicine chromosomal rearrangements chromosome aneuploidies family haplotype linkage analysis monogenic diseases preimplantation genetic testing |
| title | A comprehensive and universal approach for embryo testing in patients with different genetic disorders |
| title_full | A comprehensive and universal approach for embryo testing in patients with different genetic disorders |
| title_fullStr | A comprehensive and universal approach for embryo testing in patients with different genetic disorders |
| title_full_unstemmed | A comprehensive and universal approach for embryo testing in patients with different genetic disorders |
| title_short | A comprehensive and universal approach for embryo testing in patients with different genetic disorders |
| title_sort | comprehensive and universal approach for embryo testing in patients with different genetic disorders |
| topic | chromosomal rearrangements chromosome aneuploidies family haplotype linkage analysis monogenic diseases preimplantation genetic testing |
| url | https://doi.org/10.1002/ctm2.490 |
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