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.
A new paper in Molecular Psychiatry has been reported on extensively in the media, and readers have mentioned it several times in the comments. I read it. It’s titled Genome-wide association studies establish that human intelligence is highly heritable and polygenic. But the fact is that I read this paper last year. Back then it was titled Common SNPs explain a large proportion of the heritability for human height. I kid, but you get the picture. The new paper establishes for intelligence what we already suspected: most of the genetic variation in this heritable trait is accounted for by numerous genes of small effect. You inherit variants of these numerous genes from your two parents, and your own trait value is to a large extent a combination of the parental values. The issue is not if intelligence is heritable, but the extent of that heritability.
The Pith: In this post I examine how looking at genomic data can clarify exactly how closely related siblings really are, instead of just assuming that they’re about 50% similar. I contrast this randomness among siblings to the hard & fast deterministic nature of of parent-child inheritance. Additionally, I detail how the idealized spare concepts of genetics from 100 years ago are modified by what we now know about how genes are physically organized, and, reorganized. Finally, I explain how this clarification allows us to potentially understand with greater precision the nature of inheritance of complex traits which vary within families, and across the whole population.
Humans are diploid organisms. We have two copies of each gene, inherited from each parent (the exception here is for males, who have only one X chromosome inherited from the mother, and lack many compensatory genes on the Y chromosome inherited from the father). Our own parents have two copies of each gene, one inherited from each of their parents. Therefore, one can model a grandchild from two pairs of grandparents as a mosaic of the genes of the four ancestral grandparents. But, the relationship between grandparent and grandchild is not deterministic at any given locus. Rather, it is defined by a probability. To give a concrete example, consider an individual who has four grandparents, three of whom are Chinese, one of whom is Swedish. Imagine that the Swedish individual has blue eyes. One can assume reasonably then on the locus which controls blue vs. non-blue eye color difference one of the grandparents is homozygous for the “blue eye” allele, while the other grandparents are homozygous for the “brown eye” alleles. What is the probability that any given grandchild will carry a “blue eye” allele, and so be a heterozygote? Each individual has two “slots” at a given locus. We know that on one of those slots the individual has only the possibility of having a brown eye allele. Their probability of variation then is operative only on the other slot, inherited from the parent whom we know is a heterozygote. That parent in their turn may contribute to their offspring a blue eye allele, or a brown eye allele. So there is a 50% probability that any given grandchild will be a heterozygote, and a 50% probability that they will be a homozygote.
The above “toy” example on one locus is to illustrate that the variation that one sees among individuals is in part due to the fact that we are not a “blend” of our ancestors, but a combination of various discrete genetic elements which are recombined and synthesized from generation to generation. Each sibling then can be conceptualized as a different “experiment” or “trial,” and their differences are a function of the fact that they are distinctive and unique combinations of their ancestors’ genetic variants. That is the most general theory, without any direct reference to proximate biophysical details of inheritance. Pure Mendelian abstraction as a formal model tells us that reproductive events are discrete sampling processes. But we live in the genomic age, and as you can see above we can measure the variation in genetic relationships among siblings today in an empirical sense. The expectation, as we would expect, is 0.50, but there is variance around that expectation. It is not likely that all of your siblings are “created equal” in reference to their coefficient of genetic relationship to you.