Increased heterozygosity in low-pass sequencing data allows identification of blood chimeras in cattle

In about 90% of multiple pregnancies in cattle, shared blood circulation between fetuses leads to genetic chimerism in peripheral blood and can reduce reproductive performance in heterosexual co-twins. However, the early detection of heterosexual chimeras requires specialized tests. Here, we used low-pass sequencing data with a median coverage of 0.64× generated from blood samples of 322 F1 crosses between beef and dairy cattle and identified 20 putative blood chimeras through increased levels of genome-wide heterozygosity. In contrast, for 77 samples with routine SNP microarray data generated from hair bulbs of the same F1s, we found no evidence of chimerism, simultaneously observing high levels of genotype discordance with sequencing data. Fifteen out of 18 reported twins showed signs of blood chimerism, in line with previous reports, whereas the presence of five alleged singletons with strong signs of chimerism suggests that the in-utero death rate of co-twins is at the upper limit of former estimates. Together, our results show that low-pass sequencing data allow reliable screening for blood chimeras. They further affirm that blood is not recommended as a source of DNA for the detection of germline variants.