Reciprocal Translocation Carrier Diagnosis in Preimplantation Human Embryos.
Reciprocal Translocation Carrier Diagnosis in Preimplantation Human Embryos.
复制标题
植入前人类胚胎的相互易位携带者诊断
DOI：
10.1016/j.ebiom.2016.11.007
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发表时间：
2016-12
期刊：
影响因子：
11.1
通讯作者：
Lin, Ge
中科院分区：
文献类型：
--
作者：
Hu, Liang;Cheng, Dehua;Gong, Fei;Lu, Changfu;Tan, Yueqiu;Luo, Keli;Wu, Xianhong;He, Wenbing;Xie, Pingyuan;Feng, Tao;Yang, Kai;Lu, Guangxiu;Lin, Ge
关键词：
Preimplantation genetic diagnosis (PGD) is widely applied in reciprocal translocation carriers to increase the chance for a successful live birth. However, reciprocal translocation carrier embryos were seldom discriminated from the normal ones mainly due to the technique restriction. Here we established a clinical applicable approach to identify precise breakpoint of reciprocal translocation and to further distinguish normal embryos in PGD. In the preclinical phase, rearrangement breakpoints and adjacent single nucleotide polymorphisms (SNPs) were characterized by next-generation sequencing following microdissecting junction region (MicroSeq) from 8 reciprocal translocation carriers. Junction-spanning PCR and sequencing further discovered precise breakpoints. The precise breakpoints were identified in 7/8 patients and we revealed that translocations in 6 patients caused 9 gene disruptions. In the clinical phase of embryo analysis, informative SNPs were chosen for linkage analyses combined with PCR analysis of the breakpoints to identify the carrier embryos. From 15 blastocysts diagnosed to be chromosomal balanced, 13 blastocysts were identified to be carriers and 2 to be normal. Late prenatal diagnoses for five carriers and one normal fetus confirmed the carrier diagnosis results. Our results suggest that MicroSeq can accurately evaluate the genetic risk of translocation carriers and carrier screen is possible in later PGD treatment. MicroSeq can rapidly characterize translocation breakpoint sequences and nearby haplotype in translocation carriers. Translocation leads to frequent gene disruption in carriers with normal phenotype. MicroSeq provides sufficient information for successfully carriers screen in PGD treatment. Reciprocal translocation carriers with fertility problems could benefit from preimplantation genetic diagnosis (PGD) to select chromosomally-balanced embryos for transfer. Currently, carrier embryos and normal embryos are not routinely discriminated, mainly due to technique restriction. Theoretically, half of these offspring may inherit the infertility phenotype. Here we established a clinically applicable approach using microdissection and next generation sequencing (MicroSeq) to identify precise breakpoints and establish nearby haplotypes of derivative chromosomes. This information was used to successfully distinguish normal embryos from reciprocal translocation carrier embryos in later PGD. Our data also revealed that translocation frequently leads to gene disruption in carriers with normal phenotype.
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通讯作者：
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