Developmental pleiotropy occurs when mutations have multiple effects on the resulting phenotype. Molecular biology improved understanding of the relationship between genotype and phenotype. It is this genetic variation that underlies differences in phenotype. Supplementary epistasis occurs when two loci affect the same phenotype. Most mutations within genes are neutral, having no effect on the organism's phenotype (silent mutations). Topology is also used in evolutionary biology to represent the relationship between phenotype and genotype. Loss of p53 creates genomic instability that most often results in an aneuploidy phenotype. Unfortunately, the relationship between the phenotype and genotype of imprinted genes is solely conceptual. Oct-4 expression is associated with an undifferentiated phenotype and tumors. Cancers are known to exhibit genome instability or a mutator phenotype. Material hydrogels polarise marcrophages into the key M2 regenerative phenotype in vitro. Neoteny is not a ubiquitous trait of the human phenotype. Cancers are known to exhibit genome instability or a "mutator phenotype". The mice died prematurely from a rupture of major arteries mimicking the human vEDS phenotype. They present a characteristic facial phenotype.