Figure 1

Principle of fingerprinting parental chromosomes by genome-wide karyomapping. (a) Following single nucleotide polymorphism (SNP) genotyping of both parents and the reference (parental trio), informative SNP loci are identified for all four parental chromosomes genome-wide (chromosomes 1–6 are illustrated here) and heterozygous informative SNPs phased using the genotype of the reference DNA which can be from an existing child, sibling embryo or, as in this example, a chorion villus sample from a previous pregnancy. The details of the algorithm have been published previously¹⁶. For karyomapping, the four sets of informative SNPs for the parental chromosomes are displayed as horizontal lines (left to right, pter to qter with a gap at the centromere) and colour coded: blue and red for the paternal chromosomes and orange and green for the maternal chromosomes. The reference chromosomes are defined as blue and orange. The genotype of informative SNPs in the embryo samples (Embryos 1 and 2) is then compared to the reference and displayed in the same format. Because each gamete from the parents has a unique pattern of crossovers between the parental chromosomes, as a result of recombination in the first meiotic division, each recombinant chromosome inherited by the embryo has a correspondingly unique pattern of chromosome segments or ‘fingerprint’ from the two paternal chromosomes. In these examples, all of the chromosomes are recombinant but non-recombinant patterns are also observed. (b) Details of the karyomap fingerprint for chromosome 1 showing different patterns of chromosomal segments on both arms for the two embryos. Note that all embryo samples compared to the reference will include any crossovers in the reference sample, which the algorithm assumes is non-recombinant, in addition to any crossovers unique to that chromosome. Two of these ‘common’ crossovers for the paternal chromosome are indicated by the arrows. (c) The algorithm used to display the informative SNPs present in the embryo samples uses a rolling window and where that coincides with a crossover results in this configuration indicating the presence of both sets of informative SNPs from that parent in that window. (d) Karyomaps and fingerprints for chromosomes 1 to 6 in four single cells disaggregated from an arrested embryo. Cells 6–8 have an identical set of 7 out of the normal 12 chromosomes, whereas cell 12 has 11 chromosomes and is only missing paternal chromosome 3. The unique pattern of parental chromosome segments for each chromosome is identical in each of the single cells where the chromosomes are present. Paternal and maternal chromosomes, blue/red and orange/green horizontal lines, respectively.