Fig. 1: Embryo classification within genomic regions of consanguinity using Haploseek.

Pictured is a screen capture of chr9 haplotype data from children 2 and 3 in consanguineous family 2. The samples were derived from single cells sequenced to depth 0.2×. Maternal and paternal haplotypes are each depicted in prediction and marginal plots for each child. The prediction plot indicates the hidden Markov model (HMM) haplotype prediction (the Viterbi path) in child 2 or child 3, as indicated, relative to the affected child 1 reference (not depicted). Dark red and dark blue shaded segments indicate that child 2/3 matches child 1’s maternal and paternal haplotypes, respectively. Lighter shading indicates that child 2/3 matches the wild-type haplotypes that are not present in child 1. The marginal (posterior probability) plot indicates the degree of confidence with which the HMM is reporting a certain haplotype prediction. A marginal value of 1 means a high confidence prediction of a child 1 matching haplotype. A marginal value of 0 means high confidence prediction of a child 1 mismatching haplotype. We call sites with marginal values between 0.01 and 0.99 low confidence. These sites mostly appear near meiotic recombination sites. The marginal probabilities are plotted as dots at the single-nucleotide polymorphism (SNP) sites on the arrays that were also successfully sequenced. Green dots flag a region of consanguinity (ROC), in which the parents share both of their haplotypes (and those haplotypes are not identical to one another). Note that there is a single ROC that extends over the centromere (the centromere appears as a thin black line with no sequenced array SNPs toward the middle of the chromosome). The “show diff” checkbox on the top left is unchecked, thereby indicating that conventional Haploseek haplotype predictions are being viewed. The plot suggests two crossovers in the mother, within the ROC, upstream and downstream of the centromere in both child 2 and child 3, with low-confidence marginal scores. Thus, from this plot alone it is impossible to determine whether the mother’s paternal or maternal haplotype was transmitted to the embryo in close proximity of the maternal crossover sites. However, as long as the paternal wild-type haplotype was transmitted, the embryo could be transferred. The purple rectangle indicates an evaluation region where child 1 is H1H1 and both parents are H1H2. Regions such as these are best interpreted in the diff plot (see Fig. 2).