T2T-YAO: A Telomere-to-telomere Assembled Diploid Reference Genome for Han Chinese

Genomics Proteomics Bioinformatics. 2023 Dec;21(6):1085-1100. doi: 10.1016/j.gpb.2023.08.001. Epub 2023 Aug 16.


Since its initial release in 2001, the human reference genome has undergone continuous improvement in quality, and the recently released telomere-to-telomere (T2T) version - T2T-CHM13 - reaches its highest level of continuity and accuracy after 20 years of effort by working on a simplified, nearly homozygous genome of a hydatidiform mole cell line. Here, to provide an authentic complete diploid human genome reference for the Han Chinese, the largest population in the world, we assembled the genome of a male Han Chinese individual, T2T-YAO, which includes T2T assemblies of all the 22 + X + M and 22 + Y chromosomes in both haploids. The quality of T2T-YAO is much better than those of all currently available diploid assemblies, and its haploid version, T2T-YAO-hp, generated by selecting the better assembly for each autosome, reaches the top quality of fewer than one error per 29.5 Mb, even higher than that of T2T-CHM13. Derived from an individual living in the aboriginal region of the Han population, T2T-YAO shows clear ancestry and potential genetic continuity from the ancient ancestors. Each haplotype of T2T-YAO possesses ∼ 330-Mb exclusive sequences, ∼ 3100 unique genes, and tens of thousands of nucleotide and structural variations as compared with CHM13, highlighting the necessity of a population-stratified reference genome. The construction of T2T-YAO, an accurate and authentic representative of the Chinese population, would enable precise delineation of genomic variations and advance our understandings in the hereditability of diseases and phenotypes, especially within the context of the unique variations of the Chinese population.

Keywords: Diploid; Han Chinese; Haplotype-resolved assembly; Reference genome; Telomere-to-telomere assembly.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian People* / genetics
  • China / ethnology
  • Diploidy*
  • East Asian People
  • Genome, Human* / genetics
  • Haplotypes / genetics
  • Humans
  • Male
  • Telomere* / genetics

Supplementary concepts

  • Han Chinese people