Throughout decades, scientists have gotten close to sequencing the entire human genome, but there were always a few gaps here and there until now. In a new study, scientists have achieved complete sequencing of the X chromosome from one end to the other, covering over three million previously unmapped base pairs.
Between 1990 and 2003, the Human Genome Project, consisting of an international group of scientists taking on one of the most ambitious scientific studies of all time, worked on sequencing the human genome in great detail. The results were almost a complete blueprint for the human species, covering over 92% of the human genome, with an accuracy of more than 99.99%. Later versions closed some of these gaps, but not wholly, as others remained.
The center of the chromosome is called a centromere, and the ends are known as telomeres. These are the regions that have the most significant gaps, most likely because they are categorized by vast sections of repeating sequences, which are extremely difficult to sort out.
Now, a team of geneticists has figured out how to patch these gaps up and, for the first time, successfully sequenced the entire X chromosome from telomere to telomere. In the study, published on July 14 in the journal Nature, the team didn’t sequence an X chromosome from a human cell. Instead, they studied a model genome called CHM13, which is a type of cell that contains two identical chromosomes.
One issue that held scientists back from completely sequencing the X chromosome is that traditional technology can only read short segments of DNA at a time, leaving them to piece it all together. The team relates this to “assembling a jigsaw puzzle that’s all one color.”
New techniques that read much longer sequences at a time allowed the team to finish the puzzle. One of these methods is known as “nanopore technology,” which funnels single molecules of DNA through a small hole and sequences them by spotting changes in the current flow.
Karen Miga, the study’s lead researcher, explained:
“These repeat-rich sequences were once deemed intractable, but now we’ve made leaps and bounds in sequencing technology. With nanopore sequencing, we get ultra-long reads of hundreds of thousands of base pairs that can span an entire repeat region, so that bypasses some of the challenges.”
Nanopore technology enabled the team to fill in a significant gap in the centromere, comprising around 3.1 million base pairs of repetitive DNA.
Miga added:
“We’re starting to find that some of these regions where there were gaps in the reference sequence are actually among the richest for variation in human populations, so we’ve been missing a lot of information that could be important to understanding human biology and disease.”
This X chromosome is 1 out of 24, which the project plans to map out by the end of 2020. If the project succeeds, we will have a complete human genome sequence.
