Importance of embryo aneuploidy screening in preimplantation genetic diagnosis for monogenic diseases using the karyomap gene chip

Gang Li,Jiawei Xu,Haixia Jin,Wenyan Song,Yingchun Su,Wenbin Niu,Yingpu Sun,Yihong Guo

doi:10.1038/s41598-018-21094-6

Gang Li, Jiawei Xu + Show 6 more

Open Access

https://doi.org/10.1038/s41598-018-21094-6

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Abstract

We investigated the incidence of aneuploidy in embryos from couples carrying monogenic diseases and the effect of embryo aneuploidy screening on the monogenic disease preimplantation genetic diagnosis (PGD). From November 2014 to April 2017, 36 couples carrying monogenic diseases were enrolled. The karyomap gene chip technique was used to analyze the blastocysts from the subjects and select normal embryos for transfer. A total of 43 single-gene PGD cycles were performed. A total of 687 eggs were obtained and 186 blastocysts were biopsed. After analysis via karyomap chip, 175 blastocysts received diagnostic results. In our monogenic disease PGD, 66.8% (117/175) of the embryos were diagnosed as normal or non-pathogenic (silent carriers), and 33.2% (58/175) of the embryos were diagnosed as abnormal or pathogenic. For preimplantation genetic screening (PGS), the aneuploidy rate of embryos was 22.9% (40/175). Among embryos diagnosed as normal for monogenic diseases, 26.5% (31/117) of the embryos were aneuploid and could not be transferred. Thus, approximately 1/4 of normal or non-pathogenic blastocysts diagnosed based on monogenic disease PGD were aneuploid, indicating the necessity and importance of embryo aneuploidy screening during PGD for monogenic diseases.

Highlights

Monogenic diseases refer to diseases or pathological traits controlled by a single pair of alleles
Monogenic disease preimplantation genetic diagnosis (PGD) utilizes a variety of methods
The traditional method is to apply single-cell polymerase chain reaction (PCR) and conduct linkage analysis of the short tandem repeats (STRs) related to the pathogenic locus, which requires individualized STR design for each monogenic disease[1]. This method can be applied to monogenic disease PGD only after the verification of the pedigree

Summary

Introduction

Monogenic diseases refer to diseases or pathological traits controlled by a single pair of alleles. The traditional method is to apply single-cell polymerase chain reaction (PCR) and conduct linkage analysis of the short tandem repeats (STRs) related to the pathogenic locus, which requires individualized STR design for each monogenic disease[1]. This method can be applied to monogenic disease PGD only after the verification of the pedigree. Karyomap gene chip has been used for monogenic disease PGD to avoid monogenic diseases and chromosomal anomalies, simultaneously[5] This gene chip is designed to focus on genome-wide SNPs and can simultaneously analyze nearly 300,000 SNP loci.

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