The human genome is being sequenced again 鈥� but better. A new project to read DNA from a large number of people has launched, with the aim of sequencing the 鈥減angenome鈥�, a version of the genome that reflects the full genetic diversity of our species.
The human genome, the set of DNA that every person carries in their cells, was first read or 鈥渟equenced鈥� between 1990 and 2001. However, this first genome was incomplete because many chunks couldn鈥檛 be reconstructed. Geneticists have improved it since, with , but large gaps remained.
In 2021, the reported that it had sequenced a genome from end to end, with almost no gaps. However, it employed a shortcut of sorts to do so. Normal human cells are diploid, which means they carry two copies of the genome, which can differ significantly from one another. In contrast, the cells the T2T team used had two virtually identical copies. This made it easier to reconstruct the precise sequence, but it also meant the T2T genome couldn鈥檛 reveal how DNA varies within a person.
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The members of the want to go one better than the T2T consortium by sequencing full diploid genomes. As a first step, they focused on one person鈥檚 diploid genome to find the best way to sequence it. They asked 14 different research groups around the world to sequence it as best they could, and received 23 attempts. They then evaluated the strengths and weaknesses of each attempt, before devising an optimised method that combined the best of all of them. The result was a high-quality diploid genome sequence with very few gaps.
鈥淚t鈥檚 better than the current reference [genome, published in 2017], but we also know we can do better,鈥� says of the Rockefeller University in New York.
The consortium now aims to sequence the diploid genomes of about 450 people from all around the world, which will provide a better sense not just of how DNA varies within an individual, but how it varies between individuals. 鈥淥ne of the major drivers for this whole consortium is to represent diversity in a better way than the current reference has,鈥� says of the Wellcome Sanger Institute in Hinxton, UK.
鈥淥ne of the major goals here is to create something that could be used for personalised medicine in the future,鈥� says , also of the Rockefeller University. The more accurate and complete the reference sequence is, he says, the better doctors can identify variants that contribute to people鈥檚 risk of disease. 鈥淚f the reference is erroneous to some degree, they could miss the variation that is maybe causing your tumour,鈥� he says.
Reference: bioRxiv,
