Saturday, May 28, 2022

Most complete human genome yet reveals previously indecipherable DNA

Recommendable! Until the next study! How many more decades will it take for a full and complete human genome sequence?

One may also pay attention to the very special cell line used here. I am not so sure this special cell line fully qualifies.

"When it comes to sequencing the human genome, “complete” has always been a relative term. The first one, deciphered 20 years ago, included most of the regions that code for proteins but left about 200 million bases of DNA—8% of the human genome—untouched. Even as additional genomes were “finished,” some stretches remained out of reach, because repetitive segments of DNA confounded the sequencing technologies of the time. Now, an international grassroots effort has sorted out those hard-to-read bases, producing the most complete human genome yet.
In six papers in Science, the Telomere-to-Telomere (T2T) Consortium—named for the chromosomes’ end caps—fills in all but five of the hundreds of remaining problem spots, leaving just 10 million bases and the Y chromosome only roughly known. ...
The previously indecipherable sequences of the genome that have now come into clear view include the protective telomeres and the dense knobs called centromeres, which typically reside in the middle of each chromosome and help orchestrate its replication. Also almost completely revealed are the short arms of the five chromosomes where centromeres are skewed toward one end. Those short arms were known to contain scores of genes coding for the backbone of ribosomes, the cell’s protein factories. ...
To simplify the task, they decided to use an anonymized cell line that was derived more than 20 years ago from an unusual growth excised from the uterus of a woman—a failed pregnancy called a mole, produced when a sperm entered an egg that lacked its own set of chromosomes. With just the sperm’s genetic material, such eggs can’t develop into an embryo, but they can still replicate, especially if the sperm delivers an X instead of Y chromosome. In a boon for the project, both members of the resulting cell line’s 23 pairs of chromosomes are identical. ...
The short chromosome arms held another surprise. As expected, they included multiple copies, 400 in all, of the genes coding for the RNA that’s used to make ribosomes. ...
The short arms are also “just chock-full of [other] repeats,”  ... Those include mobile elements, duplicated segments and other types of repetitive DNA, as well as many copies of genes from other parts of the genome. ... In five spots along these chromosomes, the resulting jumble is so long that the researchers still can’t clearly determine the order of the bases, although they have a rough idea of the sequence ...
Short arms are likely hotspots for gene evolution ... as gene copies parked there are free to mutate and take on new functions. The catalog of duplications could also shed light on neurological and developmental disorders, which have been linked to variations in the number of copies of specific sequences ..."

Most complete human genome yet reveals previously indecipherable DNA | Science | AAAS Unusual cell line and multiple sequencing methods made advance possible

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