• Base Substitutions (Point Mutations): The substitution of one base for another. If not corrected, a base substitution will become a base-pair substitution. SNPs (single nucleotide polymorphisms) are marker point mutations that have been mapped across the human genome and are useful in hunting for unknown genes. The average human germline base substitution rate is 1.28-2.2 x 10⁻⁸/bp/generation (Lynch 2010, PNAS 107, 961; 2005, Nature 437, 69).
  
• Transitions: This is when a purine is substituted for a purine or a pyrimidine is substituted for a pyrimidine.
• Transversions: This is when a purine is substituted for a pyrimidine or a pyrimidine is substituted for a purine.
• Base Insertions and Deletions and Indels: An error of replication may add or skip a nucleotide or several nucleotides (small indels). In human, the rate of small indels (1 to 20 bp) has been estimated to be 2.94/genome/generation (Kloosterman et al. 2015, Genome Res. 25, 792).

• Replication Errors and Slippage: DNA polymerase can make various errors resulting in base substitution or insertions and deletions.

• Tautomeric Shifts: If a rare tautomer of a base is present during replication, it can result in a base substitution. (keto <--> enol and amino <--> imino)

• Chemical Modification of Bases: The bases can be chemically modified in numerous ways:
• Depurination: Some agents (like water!) cause the removal of a purine from a strand of DNA.
• Deamination: An amino group may be removed from a base.
• Oxidation: Oxygen may be added to a base.
• Alkylation: An alkyl group (hydrocarbon chain like a methane or something longer) is added by alkylation.
• Intercalation: Some chemicals can slip right between adjacent bases, causing trouble during DNA replication.

• Base Analogs: Some chemicals are so similar to natural bases that they can be incorporated in place of one of the normal bases.

• Ionizing Radiation: As described in the previous outline, ionizing radiation, like X rays, can create reactive ion pairs which in turn react with DNA to chemically modify it. X rays particularly cause DNA single-strand and double-strand breaks.

• Ultraviolet Light: UV changes DNA by creating covalent bonds (thymine dimers) between two thymines that line in sequence on a DNA strand.

• Transposons: These mobile genetic elements can insert a short DNA sequence in the DNA. (Transposons and schizophrenia)(LINES and SINES)
  

• Missense Mutation: A base substitution may result in one amino acid of the polypeptide being changed. (Sickle-cell anemia GAG --> GUG, glu --> val)
• Same Sense Mutation (Synonymous Mutation, Silent Mutation): A base substitution may result in no change in the polypeptide.
• Nonsense Mutation: A base substitution may result in premature termination of the translation of a polypeptide.
• Frameshift Mutation: An insertion or deletion of a nucleotide causes a shift in the reading frame and changes many amino acids of the polypeptide.

3' TACAAAACAGGG 5'
5' ATGTTTTGTCCC 3'