Taurine pangenome uncovers a segmental duplication upstream ofKITassociated with depigmentation in white-headed cattle

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. Through examining assembly path similarities within the graph, we 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. We show that exploiting assembly path similarities within graph pangenomes can reveal trait-associated complex structural variants.

Wisent genome assembly uncovers extended runs of homozygosity and a large deletion that inactivates the thyroid hormone responsive gene

“…We used the parental short reads to trio-bin the long reads, assigning an unknown/paternal/maternal tag to each read. Overall, the "binnability" of the wisent sample reads was 61.9%, which is low compared to the 79.9%, 85.0%, or 99.2% binnability observed for intra-breed (Braunvieh x Braunvieh) (Leonard et al, 2024), inter-breed (Rätisches Grauvieh x Simmental) (Milia et al, 2024), or inter-subspecies (Nellore x Brown Swiss [indicine x taurine]) (Leonard et al, 2022) Bos taurus crosses (Fig. 1a-d).…”