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Generic Human Project

Analyze genomes and find a base model with them
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As we are able to entirely sequence more peoples' genomes we're able to find the parts that are the same across all of them, the parts that only represent minor physical differences, and the parts that represent very unusual mutations. I propose an organization whose purpose would be to create a baseline human genome consisting of all the parts everyone has, a generic mix of individualized traits, and no significant mutations besides these.

This model could be used to repair DNA when that technology reaches full fruition.

For example a DNA sample contaminated by a virus could be returned to normal even if an adequate sample could not be found. Likewise an aging person's DNA could be reset to something before its undamaged state. Of course this wouldn't represent the person's actual DNA but the odds of a serious clash would be much lower.

Voice, Mar 04 2012

1000 genome project http://www.1000genomes.org/
[Voice, Mar 04 2012]

diverse to the core, for a reason http://www.theatlan...fect-health/252795/
[swimswim, Mar 04 2012]

23AndMe http://www.23andme.com
[theircompetitor, Mar 05 2012]

Scientists propose project to build synthetic human genome http://uk.mobile.re...eNews/idUKKCN0YO2HA
[Voice, Jun 03 2016]

[link]






       [+] ... sortof.   

       For instance having a lost limb replaced by a biological generic one instead of a mechanical prosthetic, yes ?
FlyingToaster, Mar 04 2012
  

       Well...   

       The first problem is that there is so much variation (much of it very common), and so little ability to correlate sequence with phenotype (yet), that we'd struggle to define a "generic" genome.   

       Moreover, there's no guarantee that a "generic" genome would be viable. It's quite likely that many genomic variants work well only in specific combinations and (perhaps surprisingly) just combining the commonest variants would lead to a non-viable human.   

       Next, we have no way (nor any way in sight) to edit the genome of a human (or any other animal), except at the single-cell stage. So, you could in theory create a human with the "generic" or "flawless" genome, but you couldn't do much for an adult human. That said, we can do very limited engineering on limited numbers of certain types of cells, and maybe in 50 years time we'd be able to edit the genome in all the cells of an adult.   

       Finally, there's another bombshell waiting to go off in the human genome. It's always assumed that your genome is the same in all your cells (barring accidental damage), but this is going to turn out not to be the case. There's already evidence for quite extensive variation between the genomes of different tissues in the same individual - probably caused by mutations during early development.   

       Over the next five years, we will discover that this variation is not only significant for some diseases, but I believe we will also find some instances where the genome is systematically "edited" in some cell-types as a method of regulation. Nature uses every other trick to regulate genes, and she will surely use this one too. (It's well- known in antibody-producing cells; but so far this is considered to be the only instance.)   

       This somatic genomic variation will add an entire new dimension to the genome, and will multiply the problems of genetic engineering exponentially.   

       Having said all that, the basic idea of finding problematic mutations (inherited or acquired) and fixing them is the essence of genomic therapies, and is being actively pursued.   

       [ ], because it's an interesting and valid idea, but also a very well-worn one.
MaxwellBuchanan, Mar 04 2012
  

       //Over the next five years, we will discover//   

       Who are you? When did you come from?
Voice, Mar 04 2012
  

       //Who are you? When did you come from?// Just trust me on this one.
MaxwellBuchanan, Mar 04 2012
  

       //Moreover, there's no guarantee that a "generic" genome would be viable. It's quite likely that many genomic variants work well only in specific combinations and (perhaps surprisingly) just combining the commonest variants would lead to a non-viable human.//   

       Even though I do know something about who Max is and where he comes from, I think he's laying it on a little bit thick here.   

       While I don't doubt that there are incompatibilities between occasional rare alleles, or even between common variants in very isolated populations, I can't imagine that there are strong incompatibilities between the commonest variants of any gene in any combination. The selection pressure against would be strong.
Loris, Mar 04 2012
  

       Yes, fair point. On the other hand, the great majority of pregnancies don't go very far beyond fertilization. There are also many couples who can't conceive for reasons unknown, and many others who have to try an inordinately large number of times to get it to work. I can't prove it, but I believe that in the interplay of 27,462 genes there are some combinations that just don't work, even though all the genes are fine in other contexts. Selection during early development just hides nature's blushes.   

       It's not so much about specific allele incompatibilities (though those will exist). It's more to do with the fact that the cell is a sort of turbulent system, and there are only so many ways in which it can settle down into a viable state.
MaxwellBuchanan, Mar 04 2012
  

       Though I base this on nothing but gut feeling, I think [MaxB]'s statements may be a bit on the conservative side. Human understanding and exploration of the fundamental properties of our bodies and minds, our environment, and our very existence are expanding at a rate unforseeable just a generation ago. Things that amaze my parents, I take for granted. Things that amaze me appear so frequently that I, a fiction writer with an imagination that knows no boundary, cannot begin to concieve what wonders my unborn children will someday take for granted. Therefore, [Max]'s rather understated revelations concerning the human genome seem perfectly logical to me.
Alterother, Mar 04 2012
  

       The somatic variation stuff is real (there are already some clues to it); the non-viability of a "majority genome" is just a gut feeling.   

       And as regards my comments on the impossibility of editing the genome in all the cells of an adult human, well, one day...   

       Mitochondria might be a good place to start. They've got a tiny genome that causes an inordinate amount of trouble, and one can at least conceive of the vaguest chance of a remote possibility of "correcting" the mitochondrial genomes in a large number of cells.
MaxwellBuchanan, Mar 04 2012
  

       hmm... if there's no generic human genome, then our ancestors are different genomes of prehistoric apes.
FlyingToaster, Mar 04 2012
  

       //I can't imagine that there are strong incompatibilities between the commonest variants of any gene in any combination.// Such incompatabilities exist: the term to Google is "double heterozygote"   

       //an interesting and valid idea, but also a very well-worn one// This idea resembles Francis Galton's multiply- exposed photographic portraits purporting to show "typical" physiognomy of various races.
mouseposture, Mar 04 2012
  

       //<me>I can't imagine that there are strong incompatibilities between the commonest variants of any gene in any combination.//
//<mouseposture>Such incompatabilities exist: the term to Google is "double heterozygote"//
  

       To be honest I don't think I said what you think I said.   

       //It's not so much about specific allele incompatibilities (though those will exist). It's more to do with the fact that the cell is a sort of turbulent system, and there are only so many ways in which it can settle down into a viable state.//   

       I certainly don't disagree that there may be strange and random interplay between the numerous elements involved. However, my take on it is that genes have evolved to cope with the constant mixing which occurs. The genes which do well tend to be the ones which play nicely with others.   

       I am not a human geneticist, but my understanding is that humans are not even a particularly genetically diverse species, taken in the round.
I say in the round because not one but two recent reports reveal that people in some existing populations carry sequence from other human 'species'[1] (Neanderthals and Denisovans). Brilliant. Now if that's possible think what itmeans for the piffling intra-species variation (within Homo sapiens sapiens).
  

       [1] The term species becomes a nebulous concept indeed.
Loris, Mar 04 2012
  

       //The genes which do well tend to be the ones which play nicely with others.// Yes, that's a fair point, and you may be right.
MaxwellBuchanan, Mar 05 2012
  

       The Halfbakery always feels a bit weird when someone annotates an idea in such a way that suggests they know what they're talking about.
hippo, Mar 05 2012
  

       If you like, I can take over for a while. I have no fucking clue what most of this recent stuff is about.
Alterother, Mar 05 2012
  

       Well based on the TV observation that O- blood (or possibly + or maybe neutral... or another letter... anyways...) can be transfused to anybody, we can start there: we want the genes that make O- blood.   

       Now is there a DNA combination for an organ that won't be rejected by anybody (or antibody as the case may be :) ? or possibly a compromise where we can permanently "dumb down" a body's antibodies a bit to meet a generic'ish DNA skin graft or something.
FlyingToaster, Mar 05 2012
  

       I'm curious as to whether or not a person composed of entirely generic dna would look like Mitt Romney.
RayfordSteele, Mar 05 2012
  

       O-neg is the universal donor. O-pos can go to anyone but an O-neg. My mother is O-neg, my father AB. Both T.G.F.J. and I are O-pos. Neither of her parents are O- anything. I don't know for certain, but this suggests to me that the O blood type is recessive--very hard to breed for.   

       The Red Cross calls us 'type-O heros' (sic) and is constantly hassling us to donate with letters and phone calls, which I frequently do even though I find the moniker vaguely insulting, as well as the 'Gallon Donor' certificates and lapel pins they send me every so often. I don't see what's so heroic about being born with a useful blood type.
Alterother, Mar 05 2012
  

       [theircompetitor] that link is incredible. I knew it was coming but I didn't know it had arrived already.
Voice, Mar 05 2012
  

       //suggests to me that the O blood type is recessive//   

       It is. "A" and "B" are two different antigens - I think they're carbohydrate groups - stuck on the surface of the red blood cells. The Rhesus factor is another antigen.   

       So, an "O negative" donor simply has neither the A nor B antigens, nor the Rhesus factor, meaning that their blood won't be recognized as "foreign" by anyone else's immune system.   

       Conversely, "AB positive" blood has all three antigens (A, B and Rhesus). Therefore, if it goes into someone who is not AB positive (for instance, they're A positive), then at least one of the three antigens (B, in this example) will be seen as "foreign" and will provoke an immune attack.   

       If I recall correctly, having even a single copy of the gene for, say "A" will result in the A-antigen being on your blood cells; likewise for "B" and Rhesus. Therefore, the only way to make an "O negative" person is for them to not inherit any of the A,B or Rhesus genes from either parent. In other words, O-negative is recessive at all three genes.   

       It's easier if you use capital letters to represent the presence of the gene or of the antigen, and lowercase to represent the absence of the gene or of the antigen. In that case, genotypes AABBRR, AaBBRR, AABbRR, AABBRr, AaBbRR, AaBbRR and AaBbRr will all be phenotypically "ABR" (AB positive in the customary notation). The only genotype which will produce an "O negative" person is aabbrr.   

       [Edit: a quick check on Wikipedia shows that there are actually a bunch of different antigens in the "Rhesus" group, but only one of the, RhesusD, is usually important.   

       I'm also puzzled by something. Incompatibility of A, B or Rhesus blood grouping can be bad in transfusions. But only Rhesus (not the A/B antigens) causes problems during childbirth, if the baby is Rhesus positive and the mother is Rhesus negative. I don't know why similar problems don't arise if the baby is, say A and the mother is O or B.
MaxwellBuchanan, Mar 05 2012
  

       The ABO blood group system isn't quite like that, Max; it's multiple alleles at the same locus. A and B are co-dominant, O is recessive.
So the possible genotypes are : AA, AO, BB, BO, AB and OO. The first two are phenotypically A, the next two are phenotypically B, the fifth is phenotypically AB and the last type O.
  

       Regarding why ABO typing doesn't usually cause problems in pregnancy, apparently antibodies against these antigens are predominantly of a type which do not cross the placenta. Antibodies against the Rhesus D factor are of a different type which can cross the placenta.
Loris, Mar 06 2012
  

       //It's multiple alleles at the same locus// D'oh! You're right, I am being a nidiot.
MaxwellBuchanan, Mar 06 2012
  
      
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