Novel PGD strategy based on single sperm linkage analysis for carriers of single gene pathogenic variant and chromosome reciprocal translocation.
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.
['Wang|Yuqian|Y|', 'Zhu|Xiaohui|X|', 'Yan|Zhiqiang|Z|', 'Zhi|Xu|X|', 'Guan|Shuo|S|', 'Kuo|Ying|Y|', 'Nie|Yanli|Y|', 'Lian|Ying|Y|', 'Huang|Jin|J|', 'Wei|Yuan|Y|', 'Liu|Ping|P|', 'Li|Rong|R|', 'Qiao|Jie|J|', 'Yan|Liying|L|']
D004624:Embryo Transfer D005260:Female D030342:Genetic Diseases, Inborn D008040:Genetic Linkage D059014:High-Throughput Nucleotide Sequencing D006801:Humans D008297:Male D020641:Polymorphism, Single Nucleotide D011247:Pregnancy D019836:Preimplantation Diagnosis D059010:Single-Cell Analysis D013094:Spermatozoa D014178:Translocation, Genetic
PGD Reciprocal translocations Monogenic disorders NGS Sperm haplotyping