Structural and epistatic regulatory variants cause hallmark white spotting in cattle
Despite being one of the most iconic and immediately recognizable traits in domestic cattle, the variants underpinning the white-spotted coat pattern of Holstein-Friesian and related breeds remain uncharacterized. Here, we report two variants modulating these effects, comprising intronic and long-distance-acting regulatory variants of the <i>MITF</i> and <i>KIT</i> genes. We confirm causality through "Holsteinized" mouse models edited for these alleles and show that these variants are likely responsible for spotting traits in other bovine breeds. These effects include epistatic impacts on other bovine coat patterns, such as fine-scale speckling, "black socks," and reversal of the otherwise dominant, "white-face" trait characteristic of Hereford cattle.
Authors
- Richard L. Mort (ORCID: https://orcid.org/0000-0002-3566-8217)
- Richard Spelman (ORCID: https://orcid.org/0000-0002-7968-1392)
- Tracey Monehan (ORCID: https://orcid.org/0009-0003-5887-769X)
- Carole Charlier (ORCID: https://orcid.org/0000-0002-9694-094X)
- Mathew D. Littlejohn (ORCID: https://orcid.org/0000-0001-9044-047X)
- Dorian J. Garrick (ORCID: https://orcid.org/0000-0001-8640-5372)
- G.M. Worth (ORCID: https://orcid.org/0009-0006-7550-2904)
- Isabelle Gamache
- Anna Yeates (ORCID: https://orcid.org/0009-0000-8755-883X)
- Louise Brennan (ORCID: https://orcid.org/0000-0003-0324-2665)
- Russell G. Snell (ORCID: https://orcid.org/0000-0002-8166-4014)
- Chad Harland (ORCID: https://orcid.org/0000-0002-6268-0107)
- Yojiro Yamanaka (ORCID: https://orcid.org/0000-0003-1483-8691)
- Jade Desjardins (ORCID: https://orcid.org/0009-0007-7320-5815)
- Marie-Pier Cloutier (ORCID: https://orcid.org/0009-0009-8667-3997)
- Richard T. Ellison (ORCID: https://orcid.org/0000-0003-1335-9832)
- Tony Fransen
- Emma L. Wilkinson (ORCID: https://orcid.org/0000-0002-7261-3338)
- Kathryn Tiplady (ORCID: https://orcid.org/0000-0002-3307-9208)
- Lijing Tang (ORCID: https://orcid.org/0000-0001-9742-769X)
- Swati Jivanji (ORCID: https://orcid.org/0000-0001-6824-1730)
- L.R. McNaughton (ORCID: https://orcid.org/0000-0001-6194-8063)
- Christine Couldrey (ORCID: https://orcid.org/0000-0001-7410-9410)
- Mitra Cowan (ORCID: https://orcid.org/0000-0003-1327-5233)
- Catherine Gray (ORCID: https://orcid.org/0000-0002-6463-2379)
- Nobuko Yamanaka (ORCID: https://orcid.org/0000-0003-1483-8691)
- John A. A. Tabares (ORCID: https://orcid.org/0009-0000-7684-7329)
Institutions
- University of Liverpool (GB)
- University of Auckland (NZ)
- University of Liège (BE)
- Livestock Improvement Corporation (NZ)
- Institute of Genetics (CA)
- McGill University (CA)
- Massey University (NZ)
- Lancaster University (GB)
Publication Details
- Journal
- Science Advances
- Published
- 2025-11-14
- DOI
- https://doi.org/10.1126/sciadv.adt5913
- Citations
- 1
- Primary Topic
- melanin and skin pigmentation
- Type
- article
- Field-Weighted Citation Impact
- 1.15
Funders
- Massey University