Chromosome abnormalities are very frequent in early human IVF embryos and are considered the main cause of implantation failure and miscarriage. Current detection methods such as low coverage massive parallel sequencing (MPS) are fast and simple, but are unable to capture the full spectrum of chromosome abnormalities. E.g. haploidy, triploidy and uniparental disomy (UPD) are not detectable and meiotic and mitotic trisomies cannot be distinguished. Other methods, based on haplotyping (tracing chromosomes from generation to generation) can be used to detect these anomalies but large scale application is difficult as these methods require DNA from relatives of the prospective parents.
We provide a novel and innovative method called 'Analysis of Parental contribution for aneuploidy detection' or 'APCAD' to detect and quantify all types of chromosome abnormalities by calculating the proportion of maternal (and hence paternal) copies for each chromosome in an embryonic sample. Combining the detection of chromosome copy number (CN) and proportion of maternal copies (%Mat) through APCAD allows to distinguish all types of chromosomal abnormalites independent of haplotyping.
In contrast to current methods, APCAD can detect the full spectrum of chromosome abnormalities, including haploidy, polyploidy and copy number neutral anomalies (UPD). APCAD guarantees a more accurate aneuploidy detection than simple CN-based methods. Moreover, using DNA samples of the prospective couple only - no family member samples are required - APCAD differentiates mosaic from complete, maternal from paternal and mitotic from meiotic CN abnormalities. In addition, the analysis can confirm that the gametes from the prospective parents were used.
Figure: Detection of the proportion of maternal copies (%Mat) combined with copy number detection allows a more reliable detection of chromosome anomalies compared to copy number detection only. E.g. disomy and uniparental disomy can be distinguished.
View larger image: pdf fileDetection of the proportion of maternal copies.pdf (211 KB)
Figure: Genomewide APCAD graphs from a male embryo with a maternal meiotic trisomy of chromosomes 1 and 16 and a monosomy of chromosome 22 with loss of the maternal copy.
View larger image: pdf fileGenomewide APCAD graphs.pdf (1.24 MB)
Publication: APCAD: a new method for detection of aneuploidy and mosaicism in preimplantation embryos, accepted for publication in Reproductive BioMedicine Online. Read here.
Patent application pending by Vrije Universiteit Brussel, titled “METHOD FOR THE ANALYSIS OF GENETIC MATERIAL”, published as WO2021/180722. Click here.