Researchers reported the first full assembly of human chromosome 8 in Nature last week.
Despite the completion of the Human Genome Project over 20 years ago, human chromosomes have remained unfinished. This is due to large regions of identical repeats clustered within centromeres, regions of segmental duplication and acrocentric short arms of chromosomes. The presence of these gaps has limited our understanding of human genetic variation and evolution. Fortunately, the advent of long-read sequencing technologies has now enabled us to assemble these regions for the first time.
Unlike the assembly of the human X chromosome, researchers used both ultra-long Oxford Nanopore Technologies and Pacific Biosciences high-fidelity data to resolve the gaps in human chromosome 8. The entire sequence of chromosome 8 is 146,259,671 bases. In this paper, researchers reported the first complete assembly of chromosome 8. The researchers filled in the gaps of more than 3 million bases that are missing from the current reference genome.
The team resolved the sequence of five previously long-standing gaps. This included a 2.08-Mb centromeric α-satellite array, a 644-kb copy number polymorphism in the β-defensin gene cluster that is important for disease risk, and an 863-kb variable number tandem repeat at chromosome 8q21.2 that can function as a neocentromere.
The project researchers also created high quality draft assemblies of the orthologous centromeres from the chimpanzee, orangutan and macaque. This enabled the team to chart the evolutionary history of the chromosome 8 centromere. Here, the team observed a mirrored symmetry in how this centromere structure evolved from great ape ancestors. They specifically found that more ancient parts were pushed to the periphery.
This project is just one step towards fully completing human chromosome assemblies and applying this knowledge to further understand human evolution and disease.
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