Structural and epistatic regulatory variants cause hallmark white spotting in cattle

Jivanji, Swati and Wilkinson, Emma and Tang, Lijing and Tiplady, Kathryn M and Yeates, Anna and Harland, Chad and Gray, Charlotte and Couldrey, Christine and Worth, Gemma and Gamache, Isabelle and Desjardins, Jade and Tabares, John A A and Yamanaka, Nobuko and McNaughton, Lorna and Brennan, Louise and Cloutier, Marie-Pier and Cowan, Mitra and Ellison, Renae and Fransen, Tony and Monehan, Tracey and Spelman, Richard J and Snell, Russell G and Charlier, Carole and Yamanaka, Yojiro and Garrick, Dorian and Mort, Richard and Littlejohn, Mathew D (2025) Structural and epistatic regulatory variants cause hallmark white spotting in cattle. Science Advances, 11 (46): eadt5913. ISSN 2375-2548

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Abstract

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 MITF and KIT 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.

Item Type:
Journal Article
Journal or Publication Title:
Science Advances
Uncontrolled Keywords:
Research Output Funding/yes_externally_funded
Subjects:
?? geneticsphenotypequantitative trait locigenetic variationpolymorphism, single nucleotideyes - externally funded ??
ID Code:
233677
Deposited By:
Deposited On:
17 Nov 2025 11:30
Refereed?:
Yes
Published?:
Published
Last Modified:
17 Nov 2025 23:05