Work

A telomere-to-telomere genome of Holstein cattle resolves chromosome-end architecture and the genetic basis of telomere length

Year: 2026

Type: preprint

Abstract: Summary Telomeres safeguard chromosome-end integrity, yet population-scale dissection of telomere-length genetics has been largely restricted to humans. Here, we report a 3.01-Gb telomere-to-telomere (T2T) genome of Holstein cattle that resolves repeat-rich chromosome ends and centromeres and enables telomere-length quantification at single-chromosome-end resolution. Holstein chromosome ends show marked telomere-length asymmetry and end-specific variation in telomere variant repeats, subtelomeric tandem repeats, GC/CpG composition, and DNA methylation. Using sequencing-depth-corrected telomere-length phenotypes from 9,591 cows, teloGWAS identifies major loci encompassing RTEL1 , CTC1 , and TERT , while multi-tissue eQTL, sQTL, TWAS, and co-expression analyses prioritize CTC1 and implicate DNA replication, DNA repair, and stress-response networks. Together, these findings extend population-scale telomere genetics beyond humans and establish a sequence-resolved framework for chromosome-end biology and telomere-informed livestock genomics. In brief Liu et al. generate a telomere-to-telomere Holstein cattle genome and resolve chromosome-end repeat architecture. Integrating end-resolved telomere annotation with population-scale GWAS and transcriptomic analyses, they identify conserved telomere-maintenance loci and nominate CTC1 as a candidate effector gene for bovine telomere length variation. Graphical abstract Highlights Holstein_T2T resolves bovine chromosome termini and centromeres Acrocentric chromosome architecture is linked to telomere length asymmetry TVR and subtelomeric GC/CpG landscapes distinguish chromosome ends The teloGWAS identifies regulatory loci near RTEL1, CTC1 and TERT

Source: bioRxiv (Cold Spring Harbor Laboratory)

DOI: 10.64898/2026.10.10.758172