nucleotide level. We focused on the bovine genome (version 4.0), whose assembly and annotation is still ongoing. Ensembl orthology predictions from release 50 were used, as these represented the highest quality genome annotations across several mammalian species. Ensembl automatically produces orthology predictions between species and for each release of the database these predictions can be easily queried using the "BioMart" tool. A simple query to obtain the number of non-orthologous genes between the bovine and the human genome returned 5,507 out of 22,836 genes. The reverse query returned 19,811 out of 36,396 human genes with no orthologs in the bovine genome. The differences are dependent on the level and quality of annotation for the two genomes, and on the larger set of annotated human genes. In order to reduce this effect in a simple two-way comparison, the bovine and human datasets were filtered with information coming from other completed genomes, specifically mouse and dog. A total of 3,801 bovine genes had no orthologs with these three species while 1,010 human genes, with orthologs in mouse and dog, had no orthologs in cow (Figure (Figure1). 1 ). These two groups of genes were considered as the most consistent non-orthologous genes to use in further work. In the previous assembly of the cow genome (Btau 3.1, Ensembl release 49), a similar query gave almost double the number of bovine non-orthologous genes (6,247), while non-orthologous human genes were slightly fewer (865). This reflects major improvements in the bovine genome assembly and annotation between