Genome wide karyomapping for preimplantation genetic diagnosis (PGD) detects inherited chromosomal aneuploidies

Abstract

OBJECTIVE: Single nucleotide polymorphism (SNP) genotyping of parents and family members with genome wide Karyomapping enables accurate linkage based testing for inherited disease combined with detection of chromosomal aneuploidy for all chromosomes (including parental origin) for PGD from single or multiple cell biopsies. Also, only inherited trisomies or uniform monosomies are detected, avoiding errors caused by chromosomal mosaicism. Here we report preliminary data on the incidence of aneuploidy in embryos not transferred following conventional PGD cycles. DESIGN: Retrospective observational study. MATERIALS AND METHODS: PGD cycles were carried out for cystic fibrosis (CF) (two couples), Huntington's disease and a reciprocal translocation. With the patients' informed consent, DNA was extracted from blood samples and biopsied embryos which had been cryopreserved but were no longer required for therapeutic use were lysed. Whole genome amplification (WGA) was then carried out (Repli-g, GE Healthcare) and the parental genomic DNA and WGA products processed for genome-wide SNP genotyping (Human CNV370 Quad v3; Illumina). RESULTS: Four out of ten embryos which were Karyomapped, in cycles for CF and Huntington's, had inherited chromosomal aneuploidies: mat. meiosis II trisomy 9 and a mat. monosomy 6, and, mat. meiosis I trisomy 11 and a mat. meiosis I trisomy 13, respectively. None of the other six embryos examined were aneuploid although in the translocation case all embryos were confirmed to be unbalanced for the translocated chromosomes. CONCLUSIONS: Quantitative methods, like comparative genomic hybridization, may overestimate the incidence of aneuploidy because they detect both inherited aneuploidies and those arising during cleavage causing chromosomal mosaicism. Karyomapping only detects inherited trisomies and, in multiple cell samples, uniform monosomies. Nevertheless, the identification of 4/16 (25%) aneuploid embryos underlines the importance of combined testing for genetic defects and chromosomal aneuploidy.