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Exome sequencing and analysis of 450k UK Biobank participants

nature.com

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Re: Exome sequencing and analysis of 450k UK Biobank participants

#31
post #17
post #16

Earlier quoted context omitted.

FWIW the study focuses on the coding region of the human genome, i.e., the other 2%. It is also important to point out that the fraction of non-coding DNA in a genome depends on the organism and is not correlated to complexity. There are multicellular organisms with less than 5% of it as well as unicellular organisms with amounts of DNA orders of magnitude higher than humans.

the marbled lungfish has the largest recorded genome of any eukaryote. One haploid copy of this fish's genome is composed of a whopping 132.8 billion base pairs, while one copy of a human haploid genome has only 3.5 billion http://www.nature.com/scitable/topicpage/eukaryotic-genome-c...

DNA developers these days just use electron and don’t care about efficiency. That lungfish is ripe for a refactoring.

Bet I could implement a new lungfish with only a few million base pairs in a weekend.

Re: Exome sequencing and analysis of 450k UK Biobank participants

#32
post #17

Earlier quoted context omitted.

the marbled lungfish has the largest recorded genome of any eukaryote. One haploid copy of this fish's genome is composed of a whopping 132.8 billion base pairs, while one copy of a human haploid genome has only 3.5 billion http://www.nature.com/scitable/topicpage/eukaryotic-genome-c...

DNA developers these days just use electron and don’t care about efficiency. That lungfish is ripe for a refactoring. Bet I could implement a new lungfish with only a few million base pairs in a weekend.

640 kbp should be enough for anybody.

Re: Exome sequencing and analysis of 450k UK Biobank participants

#34
post #33

This is neat and will lead to a lot of interesting discoveries. Golden age for genomics is ahead.

The golden age for genomics has been “ahead” since 1990.

It’s still ahead. We just don’t know which decade will yield the eureka.

Voyages of discovery are like that.

Re: Exome sequencing and analysis of 450k UK Biobank participants

#35
post #30
post #14

Earlier quoted context omitted.

Now they call it "non-coding DNA": https://en.wikipedia.org/wiki/Non-coding_DNA

That's not what your reference says. Briefly, "non-coding" means it doesn't code for proteins, while "junk" means it serves no function at all.

When the term "junk DNA" was first used it was used for everything that didn't map to proteins, because the other functions weren't yet known.

Re: Exome sequencing and analysis of 450k UK Biobank participants

#36

Earlier quoted context omitted.

Had the exact thought when I read the headline. What arrogance. "I don't understand what these genes do. Must be junk"

Actually no, that's not the intellectual level at which any science is performed, let alone population genetics and molecular genetics. Do you perhaps see the irony in making such a grotesquely arrogant suggestion yourself? People working on population genetics and molecular genetics, who came to the conclusion that much DNA has no phenotypic relevance, were doing so based on several decades of literature and 10-20+…

> Would you care to give your own qualifications in this field?

I am a programmer, and I trust my ability to call out junk code. Except if I am reading code from someone like Carmack or Linus. In those cases, I am gonna assume whatever I don't understand is my fault. What hubris would it be for me to call Linus' code junk, even if I really can't make sense of it despite my best effort?

Same here. It's fine to say "we did our best to understand this and as far as we can tell, these genes are not utilized" to go like "yeah it's junk" is quite different. You're a mere mortal, and DNA has been the foundation of all life for millennia. You don't get to judge so easily.

Re: Exome sequencing and analysis of 450k UK Biobank participants

#37
Wow, what a time to be alive! For those who are not into bio, this type of information is invaluable for untangling the molecular mechanisms of disease and can provide important clues about where we should intervene with a small molecule or antibody drug to disrupt disease processes.

To give a coding analogy, you can think of this as trying to debug a program written in a language we can’t read. We have no idea what lines are doing what, but there are many different versions / forks of this program floating around. By looking at all the diffs and comparing the outputs, we can start to figure out what some of the code is doing, and which lines we might want to comment out to correct certain types of bugs.

Re: Exome sequencing and analysis of 450k UK Biobank participants

#38

Earlier quoted context omitted.

Actually no, that's not the intellectual level at which any science is performed, let alone population genetics and molecular genetics. Do you perhaps see the irony in making such a grotesquely arrogant suggestion yourself? People working on population genetics and molecular genetics, who came to the conclusion that much DNA has no phenotypic relevance, were doing so based on several decades of literature and 10-20+…

> Would you care to give your own qualifications in this field? I am a programmer, and I trust my ability to call out junk code. Except if I am reading code from someone like Carmack or Linus. In those cases, I am gonna assume whatever I don't understand is my fault. What hubris would it be for me to call Linus' code junk, even if I really can't make sense of it despite my best effort? Same here. It's fine to say "we…

> It's fine to say "we did our best to understand this and as far as we can tell, these genes are not utilized" to go like "yeah it's junk" is quite different.

That’s not how junk DNA was defined. Junk DNA regions have no coding regions. No genes. There’s no easily recognized feature or pattern that would allow you to derive or even propose a function, despite decades of advances in the area. In this particular example the analogy with computer code won’t take you far.

Re: Exome sequencing and analysis of 450k UK Biobank participants

#39

Earlier quoted context omitted.

Actually no, that's not the intellectual level at which any science is performed, let alone population genetics and molecular genetics. Do you perhaps see the irony in making such a grotesquely arrogant suggestion yourself? People working on population genetics and molecular genetics, who came to the conclusion that much DNA has no phenotypic relevance, were doing so based on several decades of literature and 10-20+…

> Would you care to give your own qualifications in this field? I am a programmer, and I trust my ability to call out junk code. Except if I am reading code from someone like Carmack or Linus. In those cases, I am gonna assume whatever I don't understand is my fault. What hubris would it be for me to call Linus' code junk, even if I really can't make sense of it despite my best effort? Same here. It's fine to say "we…

Have you considered that there might be methods that you are not aware of for inferring whether a region of DNA has phenotypic consequences? There’s a huge literature on this. I can’t believe you’re so arrogant as to imagine that you can just intuit the contents of that literature in a few seconds thought before writing a comment on HN.

If a section of DNA has no phenotypic consequences then that means that when we look at a sample of genomes from a population, then the stochastic process underlying the evolution of that region of the genome features random genetic drift, but natural selection is only involved via statistical associations with nearby functional regions due to limited recombination. In contrast, non-junk regions of DNA have natural selection involved directly in the stochastic process underlying their evolution. That difference gives rise to a research program where we seek to infer whether or not a region is “junk” by developing statistical models of DNA sequence evolution and fitting them to data sets comprising samples of DNA sequences from multiple individuals in a population.

That’s just one example of how the question of junk vs. non- junk is studied. There’s also comparative genomics which compares genomes of related species, taking the phylogeny into account in the analysis.

You’re not expected to know any of this; it’s evidently not your field. What is expected however, as a reader of an intelligent website such as this, is for you to understand that there might actually be an entire research field lying behind a question, and not to think that everything is so simple that you can understand it without any study at all on your part.

Re: Exome sequencing and analysis of 450k UK Biobank participants

#40

Does anyone remember the days when some geneticists were saying that 98% of DNA is "junk" DNA? When I heard it I knew it couldn't be true but it's probably going to take another 50 years to figure out how much really does get used. I can't help but suspect that a lot of the genome is a part of the boot sequence that helps you go from one cell up to all the differentiated organs and tissues and systems.

That is not bad intuition. Another analogy is that coding DNA is like all the function calls - the parts of the code that change data. Non coding DNA is like the all the flow control, conditionals, constants, etc. They don’t directly operate on the data, but have a huge impact on how the program behaves given some input.
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