Mutations

What is a mutation?
A mutation is a permanent change in the sequence of DNA. In order for an observable effect, mutations must occur in gene exons or regulatory elements. Changes in the non-coding regions of DNA (introns and junk DNA) generally do not affect function.

What causes mutations?
          Mutations can be caused by external (exogenous) or endogenous (native) factors, or they may be caused by errors in the cellular machinery. Physical or chemical agents that induce mutations in DNA are called mutagens and are said to be mutagenic.
     Exogenous factors: environmental factors such as sunlight, radiation, and smoking can cause mutations.
     Endogenous factors: errors during DNA replication can lead to genetic changes as can toxic by-products of cellular metabolism.

What are the consequences of mutations?
Mutations can be advantageous and lead to an evolutionary advantage of a certain genotype. Mutations can also be deleterious, causing disease, developmental delays, structural abnormalities, or other effects.

Types of Mutations: There are several classes of mutations described below. The original sequence is shown on the top with the mutated sequence below it. The genetic sequence is shown in black while the protein sequence is in blue. Changes in sequence are highlighted by yellow. To see what these mutations look like when sequenced, click here.

Deletion Genetic material is removed or deleted. A few bases can be deleted (as shown on the left) or it can be complete or partial loss of a chromosome (shown on right).

Frameshift The insertion or deletion of a number of bases that is not a multiple of 3. This alters the reading frame of the gene and frequently results in a premature stop codon and protein truncation.

Insertion When genetic material is put into another region of DNA. This may be the insertion of 1 or more bases, or it can be part of one chromosome being inserted into another, non-homologous chromosome.

Missense A change in DNA sequence that changes the codon to a different amino acid. Not all missense mutations are deleterious, some changes can have no effect. Because of the ambiguity of missense mutations, it is often difficult to interpret the consequences of these mutations in causing disease.

Nonsense A change in the genetic code that results in the coding for a stop codon rather than an amino acid. The shortened protein is generally non-function or its function is impeded.

Point A single base change in DNA sequence. A point mutation may be silent, missense, or nonsense.

Silent A change in the genetic sequence that does not change the protein sequence. This can occur because of redundancy in the genetic code where an amino acid may be encoded for by multiple codons.

Splice Site A change in the genetic sequence that occurs at the boundary of the exons and introns. The consensus sequences at these boundaries signal where to cut out introns and rejoin exons in the mRNA. A change in these sequences can eliminate splicing at that site which would change the reading frame and protein sequence.

Translocation A structural abnormality of chromosomes where genetic material is exchanged between two or more non-homologous chromosomes.

Deletion	Genetic material is removed or deleted. A few bases can be deleted (as shown on the left) or it can be complete or partial loss of a chromosome (shown on right).
Frameshift	The insertion or deletion of a number of bases that is not a multiple of 3. This alters the reading frame of the gene and frequently results in a premature stop codon and protein truncation.
Insertion	When genetic material is put into another region of DNA. This may be the insertion of 1 or more bases, or it can be part of one chromosome being inserted into another, non-homologous chromosome.
Missense	A change in DNA sequence that changes the codon to a different amino acid. Not all missense mutations are deleterious, some changes can have no effect. Because of the ambiguity of missense mutations, it is often difficult to interpret the consequences of these mutations in causing disease.
Nonsense	A change in the genetic code that results in the coding for a stop codon rather than an amino acid. The shortened protein is generally non-function or its function is impeded.
Point	A single base change in DNA sequence. A point mutation may be silent, missense, or nonsense.
Silent	A change in the genetic sequence that does not change the protein sequence. This can occur because of redundancy in the genetic code where an amino acid may be encoded for by multiple codons.
Splice Site	A change in the genetic sequence that occurs at the boundary of the exons and introns. The consensus sequences at these boundaries signal where to cut out introns and rejoin exons in the mRNA. A change in these sequences can eliminate splicing at that site which would change the reading frame and protein sequence.
Translocation	A structural abnormality of chromosomes where genetic material is exchanged between two or more non-homologous chromosomes.