In direct screens for suppressors of the egg-laying defect of
sel-12 presenilin mutants, we and others have identified mutations in seven strong suppressor genes and several weaker suppressor genes. The genetic mapping of new spr (suppressor of presenilin) genes has been confounded by polymorphisms in the CB4856 Hawaiian strain that modify the
sel-12 phenotype. In order to understand this effect better we have intercrossed the CB4856 background with
sel-12(
ty11)
unc-1(
e719) in an N2 background and looked for modifiers of the
sel-12 egg-laying defect. Surprisingly, we find that polymorphisms in the CB4856 background can suppress
sel-12 as well as any of the previously identified spr genes. Many intergressed lines have a temperature sensitive
sel-12 suppression phenotype. This effect is not due to polymorphisms in the known spr genes in the Hawaiian strain. However, we have identified many mutations in additional, as yet uncharacterized genes, with a temperature sensitive suppressor phenotype. By backcrossing the suppressed
sel-12(
ty11)
unc-1(
e719) strains in a partial CB4856 background to N2 three additional times, we have found that most of the suppression effect is due to interacting polymorphisms in the centers of LGI and LGIV. As the CB48456 strain is also defective in RNAi we are trying to determine if there is a link between these phenotypes.