The complete sequence of a human genome | Hacker News Reader

The complete sequence of a human genome

biorxiv.org

72 pointsamingilani6 comments

Pretty cool to see the success of PacBio (Pacific Biosciences) technology for long-read sequencing. PacBio is one of the few successful sequencing technologies using nature’s canonical high-fidelity DNA reading tool (DNA polymerase). Other successful sequencing tech uses approaches that are (ingeniously) different from how DNA is read in a living cell.

PacBio circular consensus sequencing (used here) is a clever way of performing extremely accurate single-molecule reads: the target linear DNA is joined into a circle, which is read over and over again, enabling high accuracy of each base by consensus

And it's specifically the low error rate of the HiFi sequencing that enabled this advance. The string graph collapses not just because of sequence length, but error rate that makes it impossible to distinguish repeats from each other. The 15kb reads used in this paper have just enough length and accuracy to span almost all repeats in the genome (rDNA and some centromeres excluded).

The assembly used the same conceptual foundation as the original human genome assemblies, for the curious: https://doi.org/10.1093/bioinformatics/bti1114

Can you say more about why rDNA is excluded? Does this stand for ribosomal DNA? Like the DNA that codes for rRNAs? Why is that difficult to sequence?

rDNA is repeated many many times and is located at several places in the genome. Presumably we need so many ribosomes that we need to have many copies of it or else transcribing it into rRNA would be the bottle neck in translating all mRNA. Can't have any proteins without rRNA!

Cool, I didn't know that! Do you know how many times?

Edit: 200 (http://book.bionumbers.org/how-many-ribosomal-rna-gene-copie...) and its why nucleoli are a thing. This answers so many of my questions about the nucleoli and why so much RNA modification machinery is always found there...

Two guesses. rDNA folds itself so much that it becomes hard to read. Using the ribosomes to read ribosome dna might cause the ribosomes to bind up.

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