Mutations [local] are a change in the genetic code. They can happen spontaneously and are a normal consequence of the imperfect replication machinery and a consequence of damage from environmental insults. Point mutants [local] may cause a harmless change in one amino acid residue [local] with no biological effect, they may cause a change in function, or they may cause a loss of activity with lethal consequences. Point mutants can also cause major disruptions if they introduce a premature stop codon. Other mutations [local] can delete or rearrange larger parts of the genome. Two of the best known human mutations affect the hemoblobin genes. They are sickle cell anemia [local], a point mutation, and thalassemia [local], in which a missense mutation decreases the production of one of the hemoglobin chains.