Promoters (and any non-coding regulatory sequence for that matter) are extremely sensitive to point mutations.
A really important question here is whether the causal SNPs that affect polygenic traits tend to be located in these highly sensitive sequences. One hypothesis would be that regulatory sequences which are generally highly sensitive to mutations permit the occasional variant with a small effect, and these variants are a predominant influence on polygenic traits. This would be bad news for us, since even the best available editors have non-negligible indel rates at target sites.
Another question: there tend to be many enhancers per gene. Is losing one enhancer generally catastrophic for the expression of that gene?
A really important question here is whether the causal SNPs that affect polygenic traits tend to be located in these highly sensitive sequences. One hypothesis would be that regulatory sequences which are generally highly sensitive to mutations permit the occasional variant with a small effect, and these variants are a predominant influence on polygenic traits. This would be bad news for us, since even the best available editors have non-negligible indel rates at target sites.
Another question: there tend to be many enhancers per gene. Is losing one enhancer generally catastrophic for the expression of that gene?