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Omnigenetic model for complex traits

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  1. Aug 6, 2017 #1

    Ygggdrasil

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    Related to the recent discussions on this forum about the potential for genetically engineering humans in the future, researchers from Stanford University recently published a fascinating article in the journal Cell, looking into the genetics of complex traits, like height, as well as the genetics of complex diseases, like schizophrenia, rheumatoid arthritis, and Crohn's disease. From their analysis they propose an "omnigenetic" model for complex traits:
    https://www.theatlantic.com/science/archive/2017/06/its-like-all-connected-man/530532/

    If true, the results would have important implications for understanding complex diseases like schizophrenia and for efforts to genetically engineer humans. For example, the results suggests that looking for mutations or genetic variants that predispose individuals to higher risks of complex diseases may not shed any light into the underlying biology of the disease because such studies would ultimately find that every gene is implicated in the disease. Similarly, if every gene expressed in a cell contributes to every complex trait, we should be very careful when editing any gene as there is the potential for the edit to have unintended consequences on many different traits.

    More detail about the model and the data supporting it are available in the paper cited below:

    Boyle, Li and Pritchard. 2017. An expanded view of complex traits: From polygenetic to omnigenetic. Cell 169: 1177. doi:10.1016/j.cell.2017.05.038

    Abstract:
     
  2. jcsd
  3. Aug 6, 2017 #2
    “Historically, even understanding the role of one gene in one disease has been considered a major success. Now we have to somehow understand how combinations of seemingly hundreds or thousands of genes work together in very complicated ways. It’s beyond our current ability.”
    From your first link... sounds like trying to program a computer when you know nothing of it's programming language except you have sample programs to disassemble. Sounds like it may be a few more decades before we even know where to start redefining genomes.
     
  4. Aug 6, 2017 #3

    Ygggdrasil

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    Obligatory XKCD reference:
    [​IMG]
    https://xkcd.com/1605/

    We are probably a decade or so from having the capability to synthesize genomes on the scale of the human genome (~ 3 billion base pairs). However, there is an effort underway that aims to make human-scale genome synthesis feasible in 10 years (http://engineeringbiologycenter.org/). In the meantime, researchers have already synthesized a bacterial genome as well as the genome of a baker's yeast, so these will be a good system for studying how to begin making large-scale changes to genomes. For example, researchers recently pared down the genome of a bacterium to synthesize a genome with the minimum number of genes to support life. Unfortunately, about 30% of the genes in this organism had an unknown function, so there is still a lot we need to learn.
     
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