Scientists have published the first complete, gapless sequence of a human genome, two decades
after the Human Genome Project produced the first draft human genome sequence.
According to researchers, having a complete, gap-free sequence of the roughly 3 billion
bases (or “letters”) in our DNA is critical for understanding the full spectrum of human
genomic variation and for understanding the genetic contributions to certain diseases.
The work was done by the Telomere to Telomere (T2T) consortium.
Analyses of the complete genome sequence will significantly add to our knowledge of chromosomes,
including more accurate maps for five chromosome arms, which opens new lines of research.
This helps answer basic biology questions about how chromosomes properly segregate and
divide.
The T2T consortium used the now-complete genome sequence as a reference to discover more than
2 million additional variants in the human genome.
These studies provide more accurate information about the genomic variants within 622 medically
relevant genes.
The now-complete human genome sequence will be particularly valuable for studies that
aim to establish comprehensive views of human genomic variation, or how people’s DNA differs.
Such insights are vital for understanding the genetic contributions to certain diseases
and for using genome sequence as a routine part of clinical care in the future.
Many research groups have already started using a pre-release version of the complete
human genome sequence for their research.
The full sequencing builds upon the work of the Human Genome Project, which mapped about
92% of the genome, and research undertaken since then.
Thousands of researchers have developed better laboratory tools, computational methods and
strategic approaches to decipher the complex sequence.
Six papers encompassing the completed sequence appear in Science, along with companion papers
in several other journals.
That last 8% includes numerous genes and repetitive DNA and is comparable in size to an entire
chromosome.
Researchers generated the complete genome sequence using a special cell line that has
two identical copies of each chromosome, unlike most human cells, which carry two slightly
different copies.
The researchers noted that most of the newly added DNA sequences were near the repetitive
telomeres (long, trailing ends of each chromosome) and centromeres (dense middle sections of
each chromosome).
The cost of sequencing a human genome using “short-read” technologies, which provide
several hundred bases of DNA sequence at a time, is only a few hundred dollars, having
fallen significantly since the end of the Human Genome Project.
However, using these short-read methods alone still leaves some gaps in assembled genome
sequences.
The massive drop in DNA sequencing costs comes hand-in-hand with increased investments in
new DNA sequencing technologies to generate longer DNA sequence reads without compromising
the accuracy.
Over the past decade, two new DNA sequencing technologies emerged that produced much longer
sequence reads.
The Oxford Nanopore DNA sequencing method can read up to 1 million DNA letters in a
single read with modest accuracy, while the PacBio HiFi DNA sequencing method can read
about 20,000 letters with nearly perfect accuracy.
Researchers in the T2T consortium used both DNA sequencing methods to generate the complete
human genome sequence.
The researcher says tht in the future, when someone has their genome sequenced, they will
be able to identify all of the variants in their DNA and use that information to better
guide their healthcare.
Truly finishing the human genome sequence was like putting on a new pair of glasses.
Now that we can clearly see everything, we are one step closer to understanding what
it all means.