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Comment by dogline | Hacker News Reader

Yes, and I've had a hard time parsing what's different this time than last time. Anybody?

There are telomeres and centromeres on the ends and middle of chromosomes that have really long repeating sequences, which until recently were hard to sequence. This sequenced those long sequences, from a fertilized egg that apparently didn't have any female DNA. Next steps are sequencing more individuals. If this sequencing tech gets cheap enough, individualized medicine could take a big leap forward. I hope that's a good summary.

https://www.washingtonpost.com/science/2022/03/31/human-geno...

Has no male DNA (no Y chromosome), and is completely homozygous which simplified the assembly. https://web.expasy.org/cellosaurus/CVCL_VU12

The cell was female, but due to a quirk, the DNA was all male? Or I'm not understanding what the WaPo article said. The genome does have a Y chromosome: https://www.ncbi.nlm.nih.gov/assembly/GCA_009914755.4#/def

That Y chromosome was added by applying same analysis workflow to a different biological source (CORIELL:NA24385, a NIST standard material used in the Genome in a Bottle project). The other chromosomes are all from the CHM13htert line (if you click on the individual chromosomes at your link above, you can scroll down to the "/isolate" feature to see what material the sequence was derived from). There's a long tradition of having a reference assembly be a combination of different individuals. Even the "standard" GRCh38/hg38 reference doesn't represent any single individual.

Thanks for that explanation. I wonder how much harder it'll be to sequence a heterozygous genome.

First part true.

Second part is doubtful.

Individualized medicine needs a much more robust computational framework than it current has.

Each of us has a unique genome, a unique developmental history, and has lived in a unique environment.

We are n=1 experiments. Organ culture and IPSCs are a pipe dream.

Here is our approach to addressing this barrier:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979527/

The Atlantic article is based on a preprint of one of the papers now formally published in Science. They both describe the same T2T-CHM13 assembly.

Telomeres and centromeres, major histocompatibility complex, and other highly repetitive and complex regions with segmental duplications. This stuff matters!

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