[HN Gopher] Scientists Clone Two Black-Footed Ferrets from Froze...
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       Scientists Clone Two Black-Footed Ferrets from Frozen Tissues
        
       Author : Brajeshwar
       Score  : 80 points
       Date   : 2024-11-18 15:33 UTC (5 days ago)
        
 (HTM) web link (www.smithsonianmag.com)
 (TXT) w3m dump (www.smithsonianmag.com)
        
       | MrMcCall wrote:
       | I'm curious how many defects creep into the process. I doubt the
       | scientists have any idea, and I'm pretty sure the process
       | involves a great deal of statistical inference to reconstruct the
       | genome from many, many small chunks of DNA.
       | 
       | How would they even measure their accuracy? By definition,
       | there's not even a baseline to measure against, right?
        
         | Etheryte wrote:
         | Finding out how accurate this approach is should be trivial,
         | no? Take some other baseline tissue where you know the ground
         | truth, freeze it, then follow the procedure and check what you
         | get. Do this a few times and you'll have a pretty good estimate
         | of the accuracy.
        
         | dbetteridge wrote:
         | It's an interesting question but prompts the rebuttal, isn't
         | that just how things work in nature?
         | 
         | No process is 100% clean in biology, that's how we get random
         | mutation and evolution of species
        
         | gus_massa wrote:
         | > _How would they even measure their accuracy?_
         | 
         | My guessis that they already used the same tools with sheeps or
         | rats in a freezer. Combining that info with some other tool to
         | measure how much dqmage the sample gpt [1] may give an
         | estimation.
         | 
         | [1] I guess the exact damage depends on how fast it froze and
         | the changes of tenperature and other difficut to know details.
        
         | bglazer wrote:
         | This process is called genome alignment. It's actually quite a
         | fascinating computer science problem that has received a ton of
         | study over the years. I think the classical techniques treat it
         | as a dynamic programming problem but I'm not sure how the most
         | modern alignment tools work.
         | 
         | There are a number of ways that we can check for errors. First,
         | there are many different sequencing and alignment tools, each
         | with different characteristics. For example, by cross checking
         | long read sequencing from a nanopore sequencing deveice and
         | more common Illumina paired end sequencing, we can see where
         | they agree or disagree and then further check with another
         | validated method like Sanger sequencing, if we're really
         | confused about which is correct. Also, we already know a bit
         | about biology, so we can check the sequence for obviously wrong
         | patterns. Like if our sequencing says the ferret has a mutation
         | that would destroy a critical protein's function (e.g. a
         | frameshift or premature stop codon) but the ferret looks fine,
         | then we can reasonably infer that the sequencing was wrong
         | somehow. Finally, you're right that there's not a "baseline".
         | All processes in biology are inherently lossy. That said genome
         | sequencing uses pieces of the cellular machinery (DNA
         | polymerase) that can copy gene sequences with incredibly high
         | fidelity, so we rely on biology's incredible achievement to be
         | reasonably sure that we're getting the "right" answers.
        
       | Mistletoe wrote:
       | I'm ignorant about cloning progress made since Dolly. Have they
       | made advances on the problem where the clones have accelerated
       | aging because they are made from cells that are aged?
       | 
       | >On 14 February 2003, Dolly was euthanised because she had a
       | progressive lung disease and severe arthritis.[6] A Finn Dorset
       | such as Dolly has a life expectancy of around 11 to 12 years, but
       | Dolly lived 6.5 years.
       | 
       | https://en.wikipedia.org/wiki/Dolly_(sheep)
       | 
       | Or was it even a problem at all? It seems clones made later
       | haven't had that issue? It shows the power of a meme in
       | installing that idea in the consciousness of society.
       | 
       | Google is telling me this in its AI answer.
       | 
       | >Research suggests that telomeres are rejuvenated during nuclear
       | reprogramming by somatic cell nuclear transfer (SCNT).
        
         | inciampati wrote:
         | Telomere length is dynamically regulated. It sounds like SCNT
         | does well at triggering the correct reprogramming to reset
         | epigenetic features that might have led to Dolly's troubles
         | (although it seems these were greatly overstated:
         | https://blog.cirm.ca.gov/2016/07/27/cloning-breakthrough-
         | dol...)
        
       | Keysh wrote:
       | From the linked _Washington Post_ story:  "The cloned animals
       | were made by injecting one of Willa's cells into an egg from a
       | domesticated ferret."
       | 
       | Which is kind of interesting, because domesticated ferrets are a
       | different species. (I wonder if this means the clones have
       | mitochondrial DNA from the domesticated ferret egg.)
        
         | S0y wrote:
         | I think "domesticated" in this context refers to the 24 Black-
         | Footed ferrets they initially captured.
         | 
         | "officials captured 24 ferrets and started a breeding program."
        
           | Keysh wrote:
           | Those would be "captive" ferrets, not "domesticated" ones.
           | (They want to introduce the offspring from the breeding
           | program into the wild, and have in fact done this for about
           | 10,000 offspring.)
           | 
           | This article in _Science_ about the first cloned black-footed
           | ferret (https://www.science.org/content/article/conservation-
           | first-c...) specifically says, "Cloning endangered species
           | faces unique ethical questions, as well. One is whether the
           | clone, which can hold trace DNA from its surrogate mother, is
           | actually the same as the species that researchers are trying
           | to save. For example, black-footed ferret clones are created
           | using eggs from domestic ferrets, meaning they carry that
           | species' mitochondrial DNA, which is left in the egg after
           | its nucleus is extracted."
           | 
           | (Later in the article: "... apart from her mitochondrial DNA,
           | most of which comes from her domestic mother, genetic
           | analysis shows she is 100% a blackfooted ferret".)
           | 
           | "Domestic ferret" refers to the domesticated European polecat
           | (e.g., https://www.inaturalist.org/taxa/399272-Mustela-furo).
        
         | patall wrote:
         | They do have domestic ferret mitochondria. The plan is to breed
         | them, take only the male offspring, an cross those back into
         | the original population (and thus get rid of the domestic
         | heritage again).
        
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