Insertion of an endogenous Jaagsiekte Sheep Retrovirus element into the BCO2 - gene abolish its function and leads to yellow discoloration of adipose tissue in Norwegian Splæsau (Ovis aries).

In sheep, the accumulation of carotenoids in adipose tissue leading to yellow fat is a heritable, recessive trait, that can be attributed to a nonsense mutation in the beta-carotene oxygenase 2 (BCO2) gene. However, the fact that other sheep breeds affected by yellow fat do not suffer from the reported nonsense mutation suggests that other functional mechanisms must exist. We investigated one such breed, the Norwegian spaelsau, and detected an aberration in BCO2 mRNA. Nanopore sequencing of genomic DNA revealed the insertion of a 7,9 kb endogenous Jaagsiekte Sheep Retrovirus (enJSRV) sequence in the first intron of the BCO2 gene. Closer examination of cDNA revealed that the BCO2 first exon was spliced directly into position 415 of the enJSRV-sequence, immediately downstream of a potential -AG splice acceptor site. The hybrid protein product consists of 29 amino acids coded by the BCO2 exon 1, followed by 29 arbitrary amino acid coded by the enJSRV-sequence, before a translation stop codon is reached. Considering that the functional BCO2 protein consists of 575 amino acids, it is unlikely that the 59 amino acid long BCO2/enJSRV hybrid protein can display any enzyme function. The found null-allele of BCO2 presents an alternative functional mechanism for the inactivity of BCO2 and is a perfect example for the potential of screening for structural variants using long-read sequencing data.