What is the cause of “imbalanced” linkage disequilibrium?

Question

With perfect linkage disequilibrium ($D' = 1, R^2 = 1$), you might have the following table of counts for the alleles:

    B     b
A  100    0
a    0  100

With "partial" linkage disequilibrium ($D' < 1, R^2 < 1$), you'll see something like this:

    B     b
A  100   25
a   25  100

But I've sometimes seen the following "imbalanced" linkage disequilibrium ($D' = 1, R^2 < 1$):

    B     b
A  100    0
a   50  100

What gives rise to this sort of situation, where aB occurs, but Ab never does? Is there a name for this phenomenon? Which is a better measure of linkage disequilibrium in this case, the normalized LD coefficient $D'$, or the squared-correlation $R^2$?

Answer 1

This can occur if the Ab genotype is lethal, i.e. you won't observe individuals with a Ab genotype.

Allele lethality is a common mechanisms that can explain non-mendelian inheritance of a trait.

For the question of which LD metric to use, this is tricky. Under the assumption that allele lethality is indeed at play, you observed perfect haplotypes, so D'=1 wouldn't be incorrect. Yet the correlation coefficient is also correct in the sense that SNP A is not a perfect proxy for SNP B.