A Complete Telomere-to-Telomere Diploid Reference Genome for Indian Population
Year: 2025
Type: preprint
Abstract: Human reference genomes have been instrumental in advancing genomic and biomedical research, but South and Southeast Asian populations are underrepresented, despite accounting for a large proportion of world population. As a part of effort on generating reference genomes for these populations, we present the first gapless, telomere-to-telomere (T2T) diploid genome assembly created by using a trio sample set of Indian ancestry (I002C), with NG50 of 154.89 Mb and 146.27 Mb for the maternal and paternal haplotypes, including the fully assembled rDNA array for the maternal chromosome 21 and Y chromosome. With the Merqury QVs of 82.05, 83.08 and 82.64 for the maternal, paternal and haploid assemblies respectively, I002C represents the highest-quality human genome assembled in both diploid and haploid forms to date. Compared to CHM13, the I002C genome displays substantial sequence diversity, resulting in 14,943 structural variants, including 3,236 novel variants absent from public databases. Analysis of trio-phased haplotypes further revealed elevated inter-haplotype divergence within centromeric and subtelomeric regions, along with identification of differentially methylated regions (DMRs) as candidates for novel imprinting loci. As a result of substantial SVs between them, I002C is a more suitable reference than CHM13 for the genomic analysis of South Asian samples with less reference bias and better performance in mapping and variant calling, particularly for long read sequencing data. As the first high-quality T2T diploid reference genome for Indian, the largest world's population, I002C contributes to the growing set of population-specific reference genomes and helps to overcome a significant gap in human genome diversity.
Authors: Prasad Sarashetti, Josipa Lipovac, Qi Jia, Ling Wang, Zhe Li, Lovro Vrček, Ying Chen, Fei Yao, YY Sia, Dehui Lin, Xinyi Zhang, Daniel Muliaditan, Hwee Meng Low, See Ting Leong, Chiea Chuen Khor, Eleanor Wong, Weiling Zheng, Kresimir Krizanovic, John C Chambers, William Y K Hwang, Patrick Tan, Jonathan Göke, Mile Sikic, Jianjun Liu
Institutions: Agency for Science, Technology and Research, Genome Institute of Singapore, University of Zagreb, Faculty of Electrical Engineering and Computing in Zagreb, National University of Singapore, Precision Health Research, Singapore, Nanyang Technological University, Singapore General Hospital, SingHealth Duke-NUS Academic Medical Centre, Duke-NUS Medical School, National Cancer Centre Singapore, SingHealth
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4413066967