Silent Exchange of one base for another results in same amino acid often an alteration in 3rd position of codon tRNA wobble No change in protein function Missense Exchange of one base for another results in changed amino acid transversion → exchanges a purine to a pyrimidine or a pyrimidine to a purine e.g., C → A or G → T transition → exchanges a purine for another purine or a pyrimidine to another pyrimidine e.g., A → G or C → T Variable change in protein function if the new amino acid is similar to old (leu → ile) the protein will most likely function the same if the new amino acid is different (glu → val) the protein folding/stability will likely be affected e.g., sickle-cell anemia glu → val mutation in β-globin gene Nonsense Exchange of one base for another results in a stop codon Loss of function mutation as peptide is truncated Frameshift Deletion or addition of 1 or 2 bases resulting in misreading of all nucleotides downstream Loss of function mutation as peptide is completely different Large Segment Deletion Unequal crossover at meiosis results in loss of large segment of DNA Loss of function mutation e.g., α-thalassemia deletion of α-globin gene Change at splice site Alteration in base sequence at mRNA splicing site results in altered splicing can remove parts of exon can leave parts of intron Variable effect on protein function as number of spliced amino acids varies e.g., β-thalassemia Triplet repeat expansion Expansion of short nucleotide sequence results in longer polypeptide can be in coding or noncoding region Addition of amino acids affects protein structure/folding and affects function Disease display anticipation earlier disease onset in successive generations e.g., myotonic dystrophy, Huntington's disease, and Fragile X In-frame In-frame mutations