A case report in the New England Journal of Medicine describes a pair of sesquizygotic twins, they share an identical maternal allele, but are chimeric (to different degrees) for two separately identical paternal alleles.
The initial ultrasound at 6-weeks showed monozygotic twins, but at 14 weeks it was clear that these twins were different sexes. Genome analysis showed an XX/XY chimerism ratio of 47:53 in Twin 1 and 90:10 in Twin 2. #10Xgenomics linked-read sequencing identified 715/375 regions or 14.5%/10.7% of the directly phased haplotypes, that were composed of three distinct haplotypes. The sesquizygosity is due to heterogonesis caused by of their paternal chimerism arising during zygotic division. In laymans terms “the egg was fertilised simultaneously by two sperm before it divided”. This would mean the fertilsied egg has three sets of chromosomes, which would usually be incompatible with life and embryos would not survive. But these twins are rather exceptional!
The case report is a fascinating read and the group (at Queensland University of Technology) did a lot of genomic analysis include 10XGenomics linked-read sequencing* to understand the extent of the chimerism. The 10X analysis included target enrichment using Roche NimbleGen hybridization capture for chromosomes 1, 2, 3, 5, 8, 15, and 22 to generate detailed haplotype maps.
The group also performed an analysis of 968 pairs of dizygotic twins and found no evidence for other sesquizygotic twins hilighting how rare these twins are. As we get deeper sequencing on larger numbers of individuals it may be that we find many more people who are not the usual genetic make-up.
*It is a shame they did not run PacBio and Nanopore too as the genomes would represent a real benchmarking opportunity on complex genomes. Maybe something for the future?