Disease can be transmitted in an autosomal recessive, autosomal dominant or X-linked fashion or arise de novo. I want to understand the case of a mutation that may either be autosomal recessive (homozygous or compound heterozygote i.e. one mutation in the gene from mom and a different mutation in the same gene from dad) or autosomal dominant. I’ve seen that autosomal dominant sometimes turns out to be gain of function. That means the protein might form complexes with the wildtype protein to make an overall dysfunctional complex or its hyperactive in some way and that gives rise to a disease phenotype. But most disease arising from a single gene seems to require both gene copies to be knocked out by mutation. So, my question is, is autosomal dominant pretty much always assumed to arise due to a gain-of-function effect. OR can it just be that the half the protein pool is knocked out and the disease phenotype arises because you really need the full ‘dose’ of protein. OR its rate limited in a pathway, so having only half of it debilitates the system enough to give a phenotype. I would probably imagine in this case that the protein is so important, that knocking both copies out would be lethal to the organism. So, my question is, does autosomal dominant always imply gain of function or should one also consider the possibility of insufficient protein levels giving rise to the phenotype?
thanks
noopdeloop
