A new, more complete version of the human genome is already bearing fruit after being released two months ago. It has revealed enormous amounts of genetic variation between people that couldn’t previously be detected – variation that may underlie diseases.
“There were variants that were hiding in plain sight,” says at the University of California, Davis.
Other studies suggest that the new genome will finally reveal the functions of seemingly useless “junk DNA”. This DNA is repetitive, which means it has proved difficult to study in detail before now because standard sequencing technology breaks up DNA into very small chunks that are difficult to piece together when the chunks contain repetitive genetic information and so look very similar.
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“We’ve been blind to it,” says at the University of California, Santa Cruz.
Miga is co-leader of the , which in May published the most complete sequence of the human genome to date. The new genome filled in the missing 8 per cent of the sequence, most of which is highly repetitive. It also provided a more accurate, less uncertain picture of the remaining 92 per cent of the sequence. Companion papers presented preliminary analyses of the entire genome.
Miga and her colleagues have now released another five preprints analysing the new genome. While two are mostly about checking the sequence, the others are new analyses.
In one study, Dennis and her colleagues compared the new genome with more than 3000 others, harnessing new information available in the 92 per cent of the genetic sequence that was already known. In particular, they were looking for variants – genetic sites that vary from person to person – and they identified hundreds of thousands of new ones.
Using the information in the new genome, it was also possible to improve our understanding of the genetic structure of several hundred genes, says co-author at Johns Hopkins University in Maryland. “We know there are diseases associated with those genes.”
The study also allowed the team to confirm that some genetic sites that had previously been considered as possible variants were misidentified as such because of shortcomings of the sequencing techniques previously used to study the genome, says co-author at the National Institute of Standards and Technology in Maryland. There will have been a few “false discoveries” linked to those, he says, but most geneticists already realised those regions were problematic and ignored them.
It is also now possible to study regions of the genome that are still evolving, which have previously been difficult to resolve, says co-author , also at Johns Hopkins University. These include immune system genes like those in the major histocompatibility complex (MHC), which are repetitive and frequently reshuffled. “They were completely broken in the old versions of the genome assemblies,” says McCoy.
“There is variation that we previously did not ascertain right,” says at the European Molecular Biology Laboratory in Heidelberg, Germany, who wasn’t involved in the studies. He says the biggest improvements in our clarity of the genetic sequence are in large mutations, like sections of DNA flipped end-to-end.
A second study led by at the University of Connecticut mapped sections where the same stretch of DNA is repeated over and over without interruption. The researchers identified many new repeats and even new kinds of repeats. Many of the repeats were “composites” in which several different repeats were strung together in distinctive ways.
“The thing that was the most surprising is the number of repeats and the types of complex repeats,” says O’Neill. “They’re not just random repeated sequences, they have structure, and that structure can actually impact the organisation of our genome.”
Many geneticists have long argued that much of this repetitive DNA has no function and is “junk”. However, some parts do seem to play roles – for instance, regulating the activity of genes. . “We never really had the resource to study these sequences before,” she says, so that is why functions haven’t been found.
In the final study, Miga and her colleagues mapped regions called centromeres, which are crucial for cell division and thus cancer. “They presented the largest gaps in our previous human reference assembly,” she says. They found key sequences called alpha-satellites are frequently duplicated, creating a cluster of new copies surrounded by older, damaged copies. It isn’t clear why.
References: bioRxiv, , Ěý˛ą˛Ô»ĺ
