Search

Additional file 9: Figure S9. Genome-wide composition of blastocysts following multipolar zygotic division. Circos plots of six embryos that developed to the blastocyst stage following multipolar zygotic division in which each circle represents the interpreted genome constitution per chromosome (1 - X) of a sampled single cell. The interpreted genome spanning the largest part of the chromosome was chosen as overall interpretation per chromosome, as such, segmental chromosomal errors are not depicted. On the left of each circus plot, a picture is shown of each embryo before dissociation (not available for E26_Cross13).

Additional file 8: Figure S8. Anuclear blastomeres and fragments. A) Phylogenetic tree based on reassembled mitochondrial genomes of 11 anuclear blastomeres and two anuclear fragments, showing a common ancestor for sequenced blastomeres and fragments retrieved from the same embryo. One anuclear blastomere was not included. B) Box plots and median values of the number of raw reads per 10 Mb bin (y-axis) per chromosome (chr1 - chrX) and for the mitochondrial DNA (chrM) (x-axis) as determined by single-cell low-coverage whole-genome sequencing for 12 anuclear blastomeres and two anuclear fragments demonstrate the abundance of mitochondrial DNA. C) Identical plots as in B, excluding chr M demonstrate the presence of fragments of chromosomal fragments in three anuclear blastomeres. D) Overlay of bright field and Hoechst fluorescent image show anuclear (1) and mononucleated (2;3) blastomeres resulting from a multipolar zygotic division in three blastomeres.

Additional file 10. Review history.

Additional file 2: Figure S2. Analysis of blastomeres following multipolar zygotic division. A) Interpretation of haplarithm plots. Overview of chromosome-wise haplarithm patterns for distinct genomic constitutions (i.e. biparental disomy, paternal monosomy and paternal meiotic/dispermic uniparental heterodisomy). Corresponding whole-genome errors (i.e. biparental diploid or androgenetic) are characterized by the manifestation of those patterns throughout the (majority of the) genome. Defined single-cell BAF values of the segmented P1, P2, M1 and M2, form haplotype blocks, demarcated by pairwise breakpoints, i.e., homologous recombinations. Haplotype blocks, as well as the distance between the P1-P2 or M1-M2 in the paternal and maternal haplarithm, respectively, and the positioning of homologous recombinations, denote the origin and nature of copy number. The normalized LogR- values are integrated with haplarithm profiles for copy number profiling. Principles of interpretation are according to [64]. B) An overview of haplarithm profiles of 82 blastomeres and two fragments (grey squares) is depicted per category of whole-genome segregation profiles, as discussed in the main text. Each embryo is identified by a description at the top left of the embryo ID and cross (EmbryoID_Embryocross). At the top right, three chronological time-lapse images of the cleaving zygote are depicted. From left to right, the pictures show the initiation of the cleavage furrow, the ongoing first division and the embryo immediately after cleavage and before cell isolation (when video available). For each embryo, a schematic representation of likely steps leading to the genomic profile of each blastomere (B1-B4) or fragment (F1) is given. Chromosome-wise interpretation (1 - X) per blastomere is visualized in the bar above the haplarithm plots (see legend). Below each bar, the paternal haplarithm (pat-BAF), the maternal haplarithm (mat-BAF) and the normalized LogR values (LogR) are depicted. Paternal cross-over sites are depicted by the arrows (black, green or blue). A combination of parental cross-over sites in one blastomere or different cross-over sites in blastomeres of the same embryo uncover polyspermic fertilization or a meiotic error. Maternal cross-over sites (red, pink, orange) were only depicted in gynogenetic blastomeres and in case of whole-genome meiotic errors.