Here's what has me excited now!
Below is the phased chromosome by chromosome EA polygenic score of some
individual, Their 1.1 polygenic score gives an estimated IQ of 130.
What I found so interesting today was considering how this person might
go about making a rationale mate choice given the below polygenic scores for
their chromosomes. The strategy that I thought of was to focus only on perhaps
2 chromosomes. This person's top ranked chromosomes by the highest positive
score on any strand of the chromosome are 2,4, and 5. We can call the best two best
ones 2 and 4. What I considered today was what if this person sought out a partner
who also had a strong showing on chromosomes 2 and 4?
Why would they want to do that? Why not just try and maximize the IQ of their potential offspring?
The problem with simple global PGS maximization is that it is a highly unstable strategy. One could roll
the genetic dice in one generation and hit the jackpot or one could hit a lemon. For
all of human history we have pretty much always had a whole lot of lemons and only a few jackpots.
Regression to the mean is inevitable; success cannot be maintained through time.
Even with embryo technology we would be left with a large amount of lemonade.
What if there were an approach that could essentially ensure that over a few generations that
there would only ever be jackpots? If one were to be lucky with an embryo and hit a global jackpot,
then one could take it. Yet, one would also be guaranteed of at least a solid standup double for every
generation. Some might prefer to take the standup double that would accumulate through time
instead of a temporary home run.
With the strategy I thought of regression to the mean would no longer be inevitable. In fact, a process of
organizing the genome could develop in which regression would never occur again.
Here's how it works. So, both parents to be have strong showing on chromosomes 2 and 4.
What they want to do is hit a jackpot of two strong chromosomes 2s and two strong chromosome 4s
in an embryo. They are not focused on maximizing the overall PGS, they are only interested in
a local maximum in which they have two strong strands for two chromosomes.
1 in 16 embryos should have the good combo. When they hit the double combo
they have achieved their objective. If they achieved this early they might want to choose the embryo
with the highest PGS of the double combo.
What has happened now? Their offspring will have strong PGS on both strands of Chromosomes 2 and 4.
It no longer matters what the genotype of their gamete is. We know that 100% of the gametes will now have
a strong chromosome 2 and 4! We have loaded the dice. Every time we flip the coin it will come up heads! Great!
When their child is ready to be a parent, their child could look out for a partner who also had some complementary
pattern of genomic organization. For example, perhaps a suitable partner would also have been designed to have
a strong double combo on chromosomes 2 and 4 and this partner also had a single strong strand on chromosomes 5
and 9 that matched with the child of the first couple. Once again they could go through a round of embryo selection
and this time they would have an offspring that now had 4 chromosomes that had strong matches on both strands.
Wow! At the second generation mark what we now have is that this child when they are ready to have children
will produce gametes all of which had strong PGS scores for chromosomes 2,4,5 and 9. We have really loaded the dice.
By using this approach it is a certainty that the PGS will become more and more organized through time and the scores would
at some point be assured to greatly increase. Yet, here again the focus is no longer on seeking a partner merely with the highest
possible PGS. What is wanted instead is seeking out a partner who has the best complementary DNA.
It is remarkable how effective this strategy would be in quickly moving towards an optimization. Notice that for this person
nearly their entire positive score is being driven by the positive scores on chromosomes 2,4,5, 9,13, and 16. There are only about
10 chromosomes in this example that are driving the PGS, so after 5 generations one would have designed a genome
with strong double strands on all 10 chromosomes.
This slow and steady approach would mean that over the longer haul one would be guaranteed of achieving a high PGS
and each generation would be building towards that goal without necessarily being rigidly focused on only a short term
maximization. Short term maximization is highly unstable. One might by chance hit an embryo with an IQ of 150, though the next generation would then regress to average. The great part of the designed genome approach would be that such regressions would no longer occur.
Variations could obviously be tried. For example, some might be interested in selecting against the negative PGS scores.
Perhaps Chromosomes 3 and 14.
0.853 0.251 0.084 0.026 0.254 -0.112 -0.084 -0.231 0.066 0.261 -1.56E-17 0.247 0.041 0.111 0.039 -0.016 -0.012 -0.14 0.128 -0.042 0.031 0.077 0.038 0.072 0.087 0.031 0.144 0.087 -0.132 -0.219 -0.022 0.014 0.105 0.096 0.01 -0.051 0.004 -0.028 0.088 0.055 -0.035 -0.025 -0.025 0.013 0.044 0.025
Edited by mag1, 24 April 2018 - 01:18 AM.