Serial Translocation via Circular Intermediates Underlies Color Sidedness in Cattle

Color-sidedness is a dominantly inherited phenotype of cattle characterized by the polarization of pigmented sectors on the flanks, snout and ear tips.  It is also referred to as “lineback” or “witrik” (litt.: white back) as color-sided animals typically display a white band along their spine.  Color-sidedness is documented at least since the Middle Ages and is presently segregating in several cattle breeds around the globe including Belgian Blue and Brown Swiss.  We herein report the remarkable observation that color-sidedness is determined by (i) a first allele on chromosome 29 (Cs₂₉), that results from the translocation of a 492-kb chromosome 6 segment encompassing KIT to chromosome 29, and (ii) a second allele on chromosome 6 (Cs₆), derived from the first by repatriation of fused 575-kb chromosome 6 and 29 sequences to the KIT locus. We provide evidence that both translocation events involved circular intermediates.