Implications of the first complete human genome assembly
This extract was created in the absence of an abstract.
The Telomere-to-Telomere (T2T) Consortium has recently announced the assembly and analysis of the first complete human genome assembly. The use of the functionally haploid CHM13hTERT cell line (CHM13), originally isolated from a hydatidiform mole, as well as ultra-long Oxford Nanopore Technologies (ONT) and Pacific Biosciences (PacBio) high-fidelity (HiFi) data, has resulted in the gapless assemblies of all 22 autosomes plus Chromosome X, including the centromeric regions, the short arms of five acrocentric human chromosomes, and almost 200 million base pairs of novel sequence, potentially harboring protein-coding genes.
In anticipation of the initial publications, the Editors of Genome Research invited researchers in diverse fields to share with us their viewpoints on the implications of the T2T-CHM13 assembly. We asked them to elucidate the biological questions that perhaps can now be answered with the new complete assembly, especially in areas of their expertise, and why it is important from their academic perspectives.
Can Alkan1: The complete assembly generated by the T2T Consortium has several implications in my research, namely algorithm development for genomics. First of all, the gaps in the Genome Reference Consortium Human Build 38 (GRCh38) assembly are problematic because any reads that originated from those regions remain unmapped, or due to the repeats in those regions, the reads map to incorrect paralogs. This in turn causes both missing real variants due to lack of information and generation of false positive calls within the wrong paralog. The problem of lower accuracy in structural variation discovery is even more pronounced than that of single nucleotide variation and small indels. A reference genome with no gaps would therefore limit such mapping errors and improve both precision and recall of any genome variation discovery. Eliminating such problems is important in our pursuit for precision medicine. It was recently demonstrated that using the …
