Expanded application of whole-genome haplotype analysis based on SNP-array in preimplantation genetic testing for pathogenic small copy number variations
Objective:To explore the feasibility and effectiveness of whole-genome haplotype analysis based on single nucleotide microarray technology(SNP-array)in preimplantation genetic testing(PGT)for less than 5 Mb of pathological copy number variations(CNV).Methods:Couples who sought for PGT due to pathogenic small CNVs at the Reproductive Center of the First Affiliated Hospital of Sun Yat-sen University from May 2020 to November 2023 were recruited.The blastocysts fertilized through conventional ICSI were biopsied,and the biopsied samples were subjected to whole-genome amplification and SNP-array detection.The family haplotype was constructed,and the embryo haplotype was compared with the haplotype of the reference carrying the small pathogenic CNV in the family to determine whether the embryo carried the risk haplotype in the area the CNVs located for evaluating whether the embryo carried the small pathogenic CNVs.Results:A total of 14 PGT cycles were completed,and 71 embryos were biopsied.A total of 39 embryos were determined as unaffected,29 as affected,and three as X-linked carriers.In 9 embryos transferred,clinical pregnancies successfully achieved in six transfer cycles,and 5 had undergone amniocentesis.The results showed that no pathogenic CNVs inherited from the previous generation were found.Three babies were born alive and all have been shown to be in good health during postnatal follow-up so far.The results of prenatal diagnosis in all families were consistent with the results of embryo testing.Conclusions:Whole-genome haplotype analysis based on SNP-array is efficient and feasible for the detection of small pathogenic CNV lower than the range of preimplantation aneuploidy screening(PGT-A).In addition,embryo aneuploidy screening can also be completed by quantitative analysis of SNPs at the same time.
Copy number variantsPreimplantation genetic testingSingle nucleotide polymorphism arrayHaplotype analysis
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维普
