How a "designer baby" might just work

By Razib Khan | December 29, 2011 1:41 pm

In earlier discussions I’ve been skeptical of the idea of “designer babies” for many traits which we may find of interest in terms of selection. For example, intelligence and height. Why? Because variation on these traits seems highly polygenic and widely distributed across the genome. Unlike cystic fibrosis (Mendelian recessive) or blue eye color (quasi-Mendelian recessive) you can’t just focus on one genomic region and then make a prediction about phenotype with a high degree of certainty. Rather, you need to know thousands and thousands of genetic variants, and we just don’t know them.

But I just realized one way that genomics might make it a little easier even without this specific information.


The method relies on the phenotypic correlation between relatives. Even before genomics, and genetics, biometricians could generate rough & ready predictions about phenotypic values based on parental values. The extent of the predictive power depends upon the heritability of the trait. A trait like height is ~80-90% heritable. That means that ~80-90% of the variation in the population of the trait is due to genes. The expected value of your height is strongly conditional upon the heights of your parents.

That’s all common sense. What does this have to do with genomics? Simple. You are 50% identical by descent with each parent. That means half your gene copies come from your mother and half from your father. You can’t change that unless you’re a clone. But, because of the law of segregation and recombination you are not necessarily 25% identical by descent from each grandparent! The expectation is that you’re coefficient of relatedness is 25%, but there is variation around this. A given parent either contributes their own paternal or maternal homologous chromosome. There’s a 50% chance that you’re going to inherit one or the other across your chromosomes, of independent probability. You have 22 autosomal chromosome pairs (non-sex chromosomes), so there’s a strong chance that you won’t be equally balanced between your opposite sex paternal and maternal grandparents (e.g., you have more genes identical by descent from your paternal grandfather than paternal grandmother).* Second, recombination is also going to generate new combinations. In the generation we’re concerned about this will work against the dynamic we’re relying on, by swapping segments across homologous chromosomes from the parents’ mother or father.

The ultimate logic here is to select for zygotes or gametes which are biased toward the grandparents with phenotypic values which you are interested in. To give a concrete example, if you have a parent who is moderately tall, whose own father was very tall, while the mother was somewhat short, and you want the tallest possible child, you’ll want to select zygotes with the most gene content identical by descent with the tall grandparent. The point isn’t to pick specific genetic variants, you don’t need to know that. All you know is that the tall grandfather probably had genes which resulted in a predisposition toward being tall. So just make sure that the grandchild has as much of that grandparent “in them.”

I still don’t know if this is going to be cost effective in the near term. But I began to think of it because in the near future I’ll be checking the genotype of a child who has a full pedigree of 1,000,000 SNPs of their parents and grandparents.

* Modeling it as a binomial, about 1 in 7 cases will have the expected 11 chromosomes from a focal grandparent. The standard deviation is more than 2 chromosomes. You need to have about 100 zygotes to expect to get any individuals who are 5 chromosomal units away from the expected value (i.e., the individual is 10-15% instead of 25% one grandparent, or 35-40%). Obviously you need more to be assured of getting zygotes of that value. And I neglected recombination, which would work against this, by swapping genomic regions….

CATEGORIZED UNDER: Bioethics, Quantitative Genetics
  • EcoPhysioMichelle

    This would be relatively easy for the father, not so much for the mother.

  • http://www.SNPedia.com Greg

    The heritability of 30+ traits can be found at http://www.snpedia.com/index.php/Heritability in case height isn’t the only trait of interest.

  • http://sep.stanford.edu/sep/jon/ Jon Claerbout

    Fascinating! May we reference you as the originator of this idea?

  • http://blogs.discovermagazine.com/gnxp Razib Khan

    #3, i can’t imagine someone hasn’t thought of this before, but sure.

  • marcel

    Can you define, or point me to a definition of, “quasi-Mendelian recessive” something that a lay reader can follow?

    When I google it, the entire first page of hits point to this post, with one exception, and that exception is above my head.

    Thanks

  • gaffa

    It would be interesting to see some calculations on how much design or “optimization power” you could expect to get out of this methodology.

  • AMac

    Autosomes vary in length from 51 to 245 million base pairs (cite). This should make it somewhat easier to implement Razib’s plan (cf. autosomes of equal size).

  • http://www.futurepundit.com Randall Parker

    Razib, Can one use SNP test results from, say, 23AndMe to determine which chromosomes 2 siblings (or a grandchild and grandparent) share in common? Is it easy or hard to do that?

    In theory your idea should be testable given enough SNP test results across a few generations of enough different families.

    I’m also wondering how many functionally distinct versions of each chromosome exist in all of humanity. For example, how many unique (at least in areas which affect functionality) copies of the Y chromosome are there? Surely less than the number of human males in existence. But how much less?

  • http://blogs.discovermagazine.com/gnxp Razib Khan

    Razib, Can one use SNP test results from, say, 23AndMe to determine which chromosomes 2 siblings (or a grandchild and grandparent) share in common? Is it easy or hard to do that?

    yes. 23andme kind of provides this service already. and as i said in the end of the post i’m going to do with a soon-to-be-born child who has all their grandparents typed by 23andme.

    In theory your idea should be testable given enough SNP test results across a few generations of enough different families.

    yeah. also, you can probably infer the genotypes of the grandparents if you have enough siblings, as they will vary in their inheritances from their two putative parents. you could do it will cousins too, but then you have smaller and smaller blocks of potentially common inheritance.

    For example, how many unique (at least in areas which affect functionality) copies of the Y chromosome are there? Surely less than the number of human males in existence. But how much less?

    hm. i guess you’ve had to calculate mutation rates on genic regions, and then use an assumption that most mutants are recessive in effect, and then estimate the proportion which would segregate out the recessive effect?

NEW ON DISCOVER
OPEN
CITIZEN SCIENCE
ADVERTISEMENT

Discover's Newsletter

Sign up to get the latest science news delivered weekly right to your inbox!

Gene Expression

This blog is about evolution, genetics, genomics and their interstices. Please beware that comments are aggressively moderated. Uncivil or churlish comments will likely get you banned immediately, so make any contribution count!

About Razib Khan

I have degrees in biology and biochemistry, a passion for genetics, history, and philosophy, and shrimp is my favorite food. In relation to nationality I'm a American Northwesterner, in politics I'm a reactionary, and as for religion I have none (I'm an atheist). If you want to know more, see the links at http://www.razib.com

ADVERTISEMENT

See More

ADVERTISEMENT

RSS Razib’s Pinboard

Edifying books

Collapse bottom bar
+

Login to your Account

X
E-mail address:
Password:
Remember me
Forgot your password?
No problem. Click here to have it e-mailed to you.

Not Registered Yet?

Register now for FREE. Registration only takes a few minutes to complete. Register now »