There are genes that we are very confident are not necessary for viability in the lab, either singly or in combination as “Silent” cassettes. Yeast chromosome III contains two “silent” cassettes encoding silent copies of “a” and “alpha” mating type information. This is because wild yeast contains a gene, HO, which converts the mating type in haploid yeast cells. Our laboratory strains already lack a functional HO gene and hence never interconvert. No synthetic lethality has ever been observed with mutations of HO or the silent cassettes. Previous studies have shown that the silent cassettes are dispensable for growth. Thus HO and the silent cassettes will be removed from our chromosome design. We welcome suggestions for other regions about which there is a very high level of confidence that deletion will have essentially no phenotypic consequence.