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

Liu, F.; Wang, T.; Cao, P.; Wang, W.; Fatima,; Zhang, Z.; Meng, F.; Lin, P.; Wei, Z.; Liu, J.; Wu, R.; Wang, L.; Li, Y.; Zhao, G.; Bao, X.; Sun, W.; Jiang, Y.; Wang, Y.; Li, X.

doi:10.64898/2026.10.10.758172

bioRxiv · 10.64898/2026.10.10.758172

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

Liu, F.·Wang, T.·Cao, P.·Wang, W.·Fatima,·Zhang, Z.·Meng, F.·Lin, P.·Wei, Z.·Liu, J.·Wu, R.·Wang, L.·Li, Y.·Zhao, G.·Bao, X.·Sun, W.·Jiang, Y.·Wang, Y.·Li, X.

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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.

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Liu, F., Wang, T., Cao, P., Wang, W., Fatima,, Zhang, Z., Meng, F., Lin, P., Wei, Z., Liu, J., Wu, R., Wang, L., Li, Y., Zhao, G., Bao, X., Sun, W., Jiang, Y., Wang, Y., Li, X.. 2026-10-13. A telomere-to-telomere genome of Holstein cattle resolves chromosome-end architecture and the genetic basis of telomere length. https://doi.org/10.64898/2026.10.10.758172

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