Taurine pangenome uncovers a segmental duplication upstream of KIT associated with depigmentation in white-headed cattle
OPEN ACCESS
Loading...
Author / Producer
Date
2025-04
Publication Type
Journal Article
ETH Bibliography
yes
Citations
Altmetric
OPEN ACCESS
Data
Abstract
Cattle have been selectively bred for coat color, spotting, and depigmentation patterns. The assumed autosomal dominant inherited genetic variants underlying the characteristic white head of Fleckvieh, Simmental, and Hereford cattle have not been identified yet, although the contribution of structural variation upstream the KIT gene has been proposed. Here, we construct a graph pangenome from 24 haplotype assemblies representing seven taurine cattle breeds to identify and characterize the white head-associated locus for the first time based on long-read sequencing data and pangenome analyses. We introduce a pangenome-wide association mapping approach which examines assembly path similarities within the graph to reveal an association between two most likely serial alleles of a complex structural variant 66 kb upstream KIT and facial depigmentation. The complex structural variant contains a variable number of tandemly duplicated 14.3 kb repeats, consisting of LTRs, LINEs, and other repetitive elements, leading to misleading alignments of short and long reads when using a linear reference. We align 250 short-read sequencing samples spanning 15 cattle breeds to the pangenome graph, further validating that the alleles of the structural variant segregate with head depigmentation. We estimate an increased count of repeats in Hereford relative to Simmental and other white-headed cattle breeds from the graph alignment coverage, suggesting a large under-assembly in the current Hereford-based cattle reference genome which had fewer copies. Our work shows that exploiting assembly path similarities within graph pangenomes can reveal trait-associated complex structural variants.
Permanent link
Publication status
published
External links
Editor
Book title
Journal / series
Volume
35 (4)
Pages / Article No.
1041 - 1052
Publisher
Cold Spring Harbor Laboratory Press
Event
Edition / version
Methods
Software
Geographic location
Date collected
Date created
Subject
Organisational unit
03999 - Ulbrich, Susanne / Ulbrich, Susanne
09575 - Pausch, Hubert / Pausch, Hubert
Notes
Funding
204654 - COWADAPT: Genetic variants for cattle adaptability to harsh environments uncovered through a bovine multi-assembly graph (SNF)
Related publications and datasets
Is new version of: https://doi.org/10.3929/ethz-b-000712537