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

  1. Fangyuan Liu
  2. Tao Wang
  3. Pengbo Cao
  4. Wei Wang
  5. Fatima
  6. Zhuangbiao Zhang
  7. Fanxin Meng
  8. Pengfei Lin
  9. Zhenyu Wei
  10. Jie Liu
  11. Rihan Wu
  12. Lixia Wang
  13. Yunxia Li
  14. Gaoping Zhao
  15. Xiangnan Bao
  16. Wei Sun
  17. Yu Jiang
  18. Yu Wang
  19. Xihe Li
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Abstract

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.

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

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    1. Mentioned by @biorxiv-genomic.bsky.social on Bluesky

      A telomere-to-telomere genome of Holstein cattle resolves chromosome-end architecture and the genetic basis of telomere length https://www.biorxiv.org/content/10.64898/2026.10.10.758172v1

    2. Mentioned by @biorxivpreprint.bsky.social on Bluesky

      A telomere-to-telomere genome of Holstein cattle resolves chromosome-end architecture and the genetic basis of telomere length https://www.biorxiv.org/content/10.64898/2026.10.10.758172v1

    3. Version published to 10.64898/2026.10.10.758172v1 on bioRxiv