Abstract
Colour sidedness is a dominantly inherited phenotype of cattle characterized by the polarization of pigmented sectors on the flanks, snout and ear tips1. It is also referred to as ‘lineback’ or ‘witrik’ (which means white back), as colour-sided animals typically display a white band along their spine. Colour sidedness is documented at least since the Middle Ages and is presently segregating in several cattle breeds around the globe, including in Belgian blue and brown Swiss1,2. Here we report that colour sidedness is determined by a first allele on chromosome 29 (Cs29 ), which results from the translocation of a 492-kilobase chromosome 6 segment encompassing KIT to chromosome 29, and a second allele on chromosome 6 (Cs6 ), derived from the first by repatriation of fused 575-kilobase chromosome 6 and 29 sequences to the KIT locus. We provide evidence that both translocation events involved circular intermediates. This is the first example, to our knowledge, of a phenotype determined by homologous yet non-syntenic alleles that result from a novel copy-number-variant-generating mechanism.
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Acknowledgements
This work was funded by the Walloon Direction General Operationnelle Agriculture, Resources Naturelles et Environnement (grants D31-1206 and D31-1214) and the Swiss National Science Foundation (grant 31003A_133034 to T.L.). We are grateful for the support of the GIGA-R Genomics platform, to P. Melvin, to G. Mekuriaw and staff of the Andassa livestock research center, Viking Genetics, Swissgenetics and the Schweizer Braunviehzuchtverband for their assistance in sample collection, to J. Vermeesch and B. Nowakowska for their assistance with array CGH.
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K.D. performed the PennCNV, CGH, FISH, next-generation sequencing, breakpoint, DNA sequence variant and expression analyses. W.C. performed the bioinformatic analyses of the high-throughput sequencing reads. A.H., P.H., L.H., K.O., A.S., J.S. and H.S. provided samples from colour-sided animals. C.D., S.M. and S.R. performed linkage analyses in brown Swiss animals. T.L. supervised the work in Switzerland. C.C., M.G., T.D. and Z.Z. performed the association analyses. N.A. and N.C. performed SNP genotyping. C.F. and L.K. performed amplicon sequencing. Y.K., M.L. and D.Z. provided human CNV genotype data. K.D., M.G. and C.C. analysed data and wrote the manuscript.
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This file contains Supplementary Figures 1-7 with legends, Supplementary Materials, Methods and Results, which include a table and a figure, Supplementary Tables 1-2 and additional references. (PDF 1583 kb)
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Durkin, K., Coppieters, W., Drögemüller, C. et al. Serial translocation by means of circular intermediates underlies colour sidedness in cattle. Nature 482, 81–84 (2012). https://doi.org/10.1038/nature10757
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DOI: https://doi.org/10.1038/nature10757
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