Change in nucleotide sequence causes mutation. Mutations may be due to natural cause or external factors. Errors during cell division causes misinterpretation in nucleotide sequencing causes mutation. Mutations which are passed on to next generations (hereditory) are called germ line mutation and mutations at cellular level not transmitted to next generation are called somatic mutations. Offspring those are carrying mutations from mutation-free parents are called de novo mutations. Mutations may be detrimental or beneficial. Detrimental mutations are eliminated over period of time and beneficial mutations become adapted in life as permanent during evolution.

             Neutral mutations are those which do not bring any consequences in patients’s life. In addition, there are self regulatory mechanisms such as DNA repair which do not bring any deleterious effect in organism and protects organism from disease. But still certain unnoticed or irrepairable damages, which can not be rectified by auto-regulatory mechanisms, leads cells to become malignant causing cancer.

          The sequence of a gene can be altered in a number of ways. Gene mutations have varying effects on health depending on where they occur and whether they alter the function of essential proteins. Structurally, mutations can be classified as:

            Silent mutations which code for the same amino acid

            Missense mutations which code for a different amino acid.

            Nonsense mutations which code for a stop and can truncate the protein.

              Insertions add one or more extra nucleotides into the DNA. They are usually caused by transposable elements, or errors during replication of repeating elements (e.g. AT repeats). Insertions in the coding region of a gene may alter splicing of the mRNA (splice site mutation) or cause a shift in the reading frame (frameshift) both of which can significantly alter the gene product. Insertions can be reverted by excision of the transposable element.

             Deletions remove one or more nucleotides from the DNA. Like insertions, these mutations can alter the reading frame of the gene. They are generally irreversible: though exactly the same sequence might theoretically be restored by an insertion, transposable elements able to revert a very short deletion (say 1–2 bases) in any location are either highly unlikely to exist or do not exist at all. Note that a deletion is not the exact opposite of an insertion: the former is quite random while the latter consists of a specific sequence inserting at locations that are not entirely random or even quite narrowly defined.

           Amplifications (or gene duplications ) leading to multiple copies of all chromosomal regions, increasing the dosage of the genes located within them.

           Mutations whose effect is to juxtapose previously separate pieces of DNA, potentially bringing together separate genes to form functionally distinct fusion genes (e.g. bcr-abl). These include:

           Chromosomal translocations interchange of genetic parts from nonhomologous chromosomes.

          Interstitial deletions: an intra-chromosomal deletion that removes a segment of DNA from a single chromosome, thereby apposing previously distant genes. For example, cells isolated from a human astrocytoma, a type of brain tumor, were found to have a chromosomal deletion removing sequences between the "fused in glioblastoma" (fig) gene and the receptor tyrosine kinase "ros", producing a fusion protein (FIG-ROS). The abnormal FIG-ROS fusion protein has constitutively active kinase activity that causes oncogenic transformation (a transformation from normal cells to cancer cells).

           Chromosomal inversions reversing the orientation of a chromosomal segment.

                  Loss-of-function mutations are the result of gene product having less or no function. When the allele has a complete loss of function (null allele) it is often called an amorphic mutation. Phenotypes associated with such mutations are most often recessive. Exceptions are when the organism is haploid, or when the reduced dosage of a normal gene product is not enough for a normal phenotype (this is called haploinsufficiency).

                  Gain-of-function mutations change the gene product such that it gains a new and abnormal function. These mutations usually have dominant phenotypes. Often called a neomorphic mutation.

                 Dominant negative mutations (also called antimorphic mutations) have an altered gene product that acts antagonistically to the wild-type allele. These mutations usually result in an altered molecular function (often inactive) and are characterised by a dominant or semi-dominant phenotype. In humans, Marfan syndrome is an example of a dominant negative mutation occurring in an autosomal dominant disease. In this condition, the defective glycoprotein product of the fibrillin gene (FBN1) antagonizes the product of the normal allele.

                  Lethal mutations are mutations that lead the death of the organisms which carry the mutations.

                   Morphological mutations usually affect the outward appearance of an individual. Mutations can change the height of a plant or change it from smooth to rough seeds.

                    Biochemical mutations result in lesions stopping the enzymatic pathway. Often, morphological mutants are the direct result of a mutation due to the enzymatic pathway.

      Chemicals --

                                      Ultraviolet radiation (nonionizing radiation) excites electrons to a higher energy level. DNA molecules are good absorbers of ultraviolet light, especially that with wavelengths in the 260 to 280 nm range. Two nucleotide bases in DNA – cytosine and thymine – are most vulnerable to excitation that can change base-pairing properties. UV light can induce adjacent thymine bases in a DNA strand to pair with each other, as a bulky dimer.