Protective factor outweighs the risk factor from the Neanderthal locus.
Conversely, the protective effect of the HLA-A02:01, B18:01, DRB*03:01 three-loci extended haplotype in the Sardinian population was shown to efficiently contrast the high risk of a severe and devastating outcome of the infection predicted for carriers of the Neanderthal locus [OR 15.47 (95% CI 5.8 – 41.0), p < 0.0001].
As a layperson I find these Neanderthal DNA numbers to be rather confusing. I'm confident the following is wrong somehow, and I'd love to hear why:
I've read numerous times that the average European's DNA is ~2% Neanderthal, but I've also read that the difference between the human genome and the chimp genome is only 1-4%. So, that ~4% of DNA is 'human DNA', while the rest is basically hominid boilerplate. Neanderthals were presumably similar--~95% boilerplate hominid DNA and 5% 'Neanderthal DNA'.
So, if only 4% of my DNA is 'Human DNA', and 2% of that is 'Neanderthal DNA'... wouldn't that make me half human, half Neanderthal? (i.e. 96% boilerplate, 2% human, 2% Neanderthal). My assumption here is that the 5% 'human DNA' and the 5% 'Neanderthal DNA' overlap, and so any 'Neanderthal DNA' in my genome replaced 'human DNA' as opposed to boilerplate DNA, which might be wrong, but even with zero overlap, wouldn't that make me at least one third Neanderthal, two-thirds human? (i.e. 94% boilerplate, 4% human, 2% Neanderthal)
The 2% here isn't the full thing, it's of the "highly variable genes." So if the "boilerplate" is 90% (for example) then the 2% mentioned is of that final 10%, or 0.2% of the total.
I used 90% as a simpler example, but the reality is the "boilerplate" between Neanderthals and modern humans here is closer to 98-99%, which puts that 2% at around 0.0004% to 0.0002% of the total genome.
I guess it's similar to the numbers you get for heritage; eg. you might genetically be 50% Caucasian and 50% Asian. This does not mean that Asians and Caucasians have completely different DNA
Conversely, the protective effect of the HLA-A02:01, B18:01, DRB*03:01 three-loci extended haplotype in the Sardinian population was shown to efficiently contrast the high risk of a severe and devastating outcome of the infection predicted for carriers of the Neanderthal locus [OR 15.47 (95% CI 5.8 – 41.0), p < 0.0001].
https://www.frontiersin.org/articles/10.3389/fimmu.2022.8911...