By the mid-2010s, you could genotype all the parts of a person’s DNA most likely to differ from other people’s for under $100. At that price point, it became possible to gather genomes from hundreds of thousands of people and assemble them into giant databases that researchers could access.
I think there’s a good chance that transposon count in the DNA differs between people, shotgun sequencing can’t tell you how many times a given sequence appears.
There’s a tradition in biology to consider things that can’t be easily measured as irrelevant, but that doesn’t mean it’s true.
The effect of structural variants like that would be bounded by the difference between SNP heritability and full heritability. That’s an easy measurement. (And if it was really responsible for much variance, then it ought to show up as a variance component with whole-genomes from long-read sequencing, I would think.) What evidence is there that transposon counts really matter much in terms of total variance phenome-wide?
Transposons activity is not downregulated in the placenta while being downregulated in most other cells. If there are too many transposons in the DNA that likely makes the placenta fail during the pregnancy. As a result, the amount of variance in transposon counts you see when sequencing born people is more limited than that of embryos.
If you do IVF you care about the pregnancy not terminating after three or four months.
The evidence is more of a theoretical argument. In the selfish gene frame, transposons (even when they aren’t technically genes) “benefit” from copying themselves even when it reduces the total fitness of the organism.
You need a mechanism that prevents people with too many transposons from procreating to account for transposons counts not just growing indefinitely.
In the absence of a process that regulates a quantity, you have variance. Lack of observed variance in sequenced adult genomes is evidence of a mechanism for regulation existing.
I think there’s a good chance that transposon count in the DNA differs between people, shotgun sequencing can’t tell you how many times a given sequence appears.
There’s a tradition in biology to consider things that can’t be easily measured as irrelevant, but that doesn’t mean it’s true.
The effect of structural variants like that would be bounded by the difference between SNP heritability and full heritability. That’s an easy measurement. (And if it was really responsible for much variance, then it ought to show up as a variance component with whole-genomes from long-read sequencing, I would think.) What evidence is there that transposon counts really matter much in terms of total variance phenome-wide?
Transposons activity is not downregulated in the placenta while being downregulated in most other cells. If there are too many transposons in the DNA that likely makes the placenta fail during the pregnancy. As a result, the amount of variance in transposon counts you see when sequencing born people is more limited than that of embryos.
If you do IVF you care about the pregnancy not terminating after three or four months.
The evidence is more of a theoretical argument. In the selfish gene frame, transposons (even when they aren’t technically genes) “benefit” from copying themselves even when it reduces the total fitness of the organism.
You need a mechanism that prevents people with too many transposons from procreating to account for transposons counts not just growing indefinitely.
In the absence of a process that regulates a quantity, you have variance. Lack of observed variance in sequenced adult genomes is evidence of a mechanism for regulation existing.
To the extent that transposon sequences affect traits and risks but can’t be measured we should expect that be reflected in “missing heritability”.
You may very well be right that highly repetitive sequences like transposons do affect traits, but that’s accounted for.