Entire human genome sequenced

Nearly two decades after the initial release of the human genome sequence, scientists have published the first gap-less, complete sequence.

When the Human Genome Project first released the human genome sequence in 2003, about eight percent of the sequences were still missing or ambiguous. This was partly due to the technical difficulties associated with correctly placing sequences of DNA made up of short repeats of base-pairs. Now, scientists from the international Telomere to Telomere (T2T) consortium have leveraged new sequencing technologies to solve the puzzle (see also BioNews 1098).

‘Using long-read methods, we have made breakthroughs in our understanding of the most difficult, repeat-rich parts of the human genome,' said Dr Karen Miga, investigator at the University of California, Santa Cruz, and co-chair of the T2T consortium. 'This complete human genome sequence has already provided new insight into genome biology, and I look forward to the next decade of discoveries about these newly revealed regions.'

Most of the new sequences map either telomeres, the part of the genome found at the end of the strands of DNA, centromeres, found in the middle of chromosomes, or the short arms of five acrocentric chromosomes. The latter are characterised by disproportionally short arms which make them asymmetric and code for ribosomes, which are the machinery cells use to assemble proteins. Telomeres and centromeres are also crucial for cell biology and play a key role in cell division.

The effort leading up to this new human genome reference assembly called T2T-CHM13, has recently been published in Science alongside five companion articles, that start to explore biological implications of the new data. These projects include the construction of a complete map of the epigenome, as well as using T2T-CHM13 to study genetic variability that could be relevant to diseases and their epidemiology.

The newly described highly repetitive DNA sequences are also those that are typically most variable and changing. Scientists therefore expect that the new sequence data will help advance our understanding of human evolution and speciation, including the development of higher cognitive functions.

‘Because these regions are so dynamic and changing so rapidly, there's some hope that any of the clues to what makes humans uniquely human in terms of cognition, and an increased brain size, etcetera, might have some connection to these regions that we've uncovered', explained T2T co-chair Dr Adam Philippy, from the National Human Genome Research Institute in Bethesda, Maryland, to the BBC.

The samples used to establish the new reference genome were derived from a complete hydatidiform mole, a type of non-viable pregnancy that contains two identical sets of chromosomes from the father, including an X but no Y chromosome. Researchers from the Human Pangenome team plan on sequencing a total of 350 further genomes from people from diverse ancestries, which will add to the reference sequences available.