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The complete sequence of a human Y chromosome

nature.com

181–190 of 232 posts

Re: The complete sequence of a human Y chromosome

#181
post #6

Could someone explain exactly what it means to be "completely sequence" the human genome when all humans have distinct genetic makeup (ie, different sequences of nucleobases in their DNA/RNA)?

What you are getting at is now called a “pangenome assembly”. Several high profile papers earlier this year, one by Guarracino and Garrison in Nature.

A pangenome is a complex graph model that weaves together hundreds or more genomes/haplotypes—usually of one species, but the idea can extend across species too, or even cells within one individual (think cancer pangenomes).

On the idealized human pangenome graph each human is represented by two threads along each autosome, plus threads through Chr X, Y, and the mitochondrial genome.

Re: The complete sequence of a human Y chromosome

#182
post #115
post #37

Earlier quoted context omitted.

I'm curious if these 750MB + the DNA of mitochondria + the protein metagenomics contain all the information needed to build a human, or if there's extra info stored in the machinery of the first cell. That is if we transfer the DNA to an advanced alien civilization - would they be able to make a human.

Yes, there is extra information in the first cells, in particular regulatory elements such as miRNAs. The headline here is epigenetics.

There's also some interesting work on understanding the roll of loops in the physical structure of the DNA storage on gene expression. [0] The base sequence of the DNA isn't everything; it may also matter how the DNA gets laid out in space---a feature which can be inherited.

[0] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2638769/

Re: The complete sequence of a human Y chromosome

#183

This is actually kind of a huge deal since it means that all 24 chromosomes have now been fully sequenced. As it says in the abstract, up until now the Y chromosome proved difficult to sequence due to its nature.

What makes the Y chromosome more difficult?

All of the chromosomes have difficult bits in them. The Y chromosome in particular has huge sections that are difficult.

By difficult, imagine a jigsaw puzzle. Difficult bits in the jigsaw puzzle are where you have the same sub-image repeated over and over again, or where the same image section is repeatedly scattered over the wider image. Puzzle pieces from these bits are difficult because you can't tell which part of the image such a small puzzle piece comes from, because it matches multiple places. It's technically impossible to resolve repetitive features where the repeating unit is larger than the pieces you are trying to assemble together. Modern technology gives us long read sequencing, where sequenced sections of DNA may be up to 100kbp or larger (maybe up to a 1Mbp), where older sequencing methods (that are still heavily used because they are cheaper) give us sequenced sections of DNA between 100-300bp long. (bp stands for base-pairs - one of [ACGT].) These larger puzzle pieces allowed the whole picture to be assembled without ambiguity.

However, this isn't why the Y chromosome was solved last. The reason for this is that the other chromosomes were analysed using a completely homozygous hydatidiform mole, which is where cells generate two copies of their entire genome from just one copy during conception, and therefore the two copies are identical. It makes the sequencing a lot easier if you don't have to deal with having two copies of the DNA that are slightly different. The side-effect of that is the hydatidiform mole doesn't have a Y chromosome, so they had to analyse a different sample later on to get a Y chromosome.

Re: The complete sequence of a human Y chromosome

#184
post #57
post #30

Earlier quoted context omitted.

Yes, but the HGP didn't make a full sequence either, using their scaffold-based contig assembly. Both groups declared a truce and announced they were "finished with the first draft" 35 years ago: https://www.nytimes.com/1987/12/13/magazine/the-genome-proje... 33 years ago: https://www.nytimes.com/1990/06/05/science/great-15-year-pro... 29 years ago: the competition gets fierce https://www.nytimes.com/1994/02/22/scien…

Lets not forget how Perl Saved The Human Genome Project [1], which I remember seeing in a print magazine at the time. As someone who is in the genomics world now as a software person, I find it amusing that I've gotten more into perl over the last year or so. It has its place, in the way that grep/sed/awk/etc does. [1] https://news.ycombinator.com/item?id=30327812

Hi, I'm in software and looking to get into genomics/biotech. I'd like to learn more about how you made the move. Is there a way I could dm you? I saw no email in your profile.

Re: The complete sequence of a human Y chromosome

#188
post #5

For those who don't recall: Back in the Dark Ages, there was a race to decode the human genome. The leading competitiors (wealthiest) were Celera Genomics and the Human Genome Project. After some time, Celera (headed by Craig Venter), announced they had done the deed. However, what Celera had actually done was used what they called a "shotgun method", which meant they took small samples here and there, then built a m…

My recollection of the contentious issues at the time are that a) the Celera project needed the information being made public by the NIH/international Human Genome Project in order to assemble sequences, but was keeping secret its own results, and b) it was intent on acquiring IP rights before the information entered the public domain.

Re: The complete sequence of a human Y chromosome

#190

Here is the "dumb question" I've always had about recording the human genome. We all have different DNA. So is "the human genome" some kind of "average" DNA, or is it the DNA of whoever they sampled, or is it maybe an overview of what is common for all of us?

I assume it's one person's DNA. The last time there was talk about this in popular media was the DNA of one person.
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