Gene MutationGenes are segments of DNA located on chromosomes. A gene mutation is defined as an alteration in the sequence of nucleotides in DNA. This change can affect a single nucleotide pair or larger gene segments of a chromosome. DNA consists of a polymer of nucleotides joined together. During protein synthesis, DNA is transcribed into RNA and then translated to produce proteins. Altering nucleotide sequences most often results in nonfunctioning proteins. Mutations cause changes in the genetic code that lead to genetic variation and the potential to develop disease. Gene mutations can be generally categorized into two types: point mutations and base-pair insertions or deletions.
Point MutationsPoint mutations are the most common type of gene mutation. Also called a base-pair substitution, this type of mutation changes a single nucleotide base pair. Point mutations can be categorized into three types:
- Silent Mutation: Although a change in the DNA sequence occurs, this type of mutation does not change the protein that is to be produced. This is because multiple genetic codons can encode for the same amino acid. Amino acids are coded for by three nucleotide sets called codons. For example, the amino acid arginine is coded for by several DNA codons including CGT, CGC, CGA, and CGG (A = adenine, T = thymine, G = guanine and C = cytosine). If the DNA sequence CGC is changed to CGA, the amino acid arginine will still be produced.
- Missense Mutation: This type of mutation alters the nucleotide sequence so that a different amino acid is produced. This change alters the resulting protein. The change may not have much effect on the protein, may be beneficial to protein function, or may be dangerous. Using our previous example, if the codon for arginine CGC is changed to GGC, the amino acid glycine will be produced instead of arginine.
- Nonsense Mutation: This type of mutation alters the nucleotide sequence so that a stop codon is coded for in place of an amino acid. A stop codon signals the end of the translation process and stops protein production. If this process is ended too soon, the amino acid sequence is cut short and the resulting protein is most always nonfunctional.
Base-pair Insertions/DeletionsMutations can also occur in which nucleotide base pairs are inserted into or deleted from the original gene sequence. This type of gene mutation is dangerous because it alters the template from which amino acids are read. Insertions and deletions can cause frame shift mutations when base pairs that are not a multiple of three are added to or deleted from the sequence. Since the nucleotide sequences are read in groupings of three, this will cause a shift in the reading frame. For example, if the original transcribed DNA sequence is CGA CCA ACG GCG ..., and two base pairs (GA) are inserted between the second and third groupings, the reading frame will be shifted.
- Original Sequence: CGA-CCA-ACG-GCG...
- Amino Acids Produced: Arginine - Proline - Threonine - Alanine ...
- Inserted Base Pairs (GA): CGA-CCA-GAA-CGG-CG...
- Amino Acids Produced: Arginine - Proline - Glutamic Acid - Arginine ...
Gene Mutation CausesGene mutations are most commonly caused as a result of two types of occurrences. Environmental factors such as chemicals, radiation, and ultraviolet light from the sun can cause mutations. These mutagens alter DNA by changing nucleotide bases and can even change the shape of DNA. These changes result in errors in DNA replication and transcription.
Other mutations are caused by errors made during mitosis and meiosis. Common errors that occur during cell division can result in point mutations and frame shift mutations. Mutations during cell division can lead to replication errors which can result in the deletion of genes, translocation of portions of chromosomes, missing chromosomes, and extra copies of chromosomes.
Genetic DisordersAccording to the National Human Genome Institute, most all disease have some sort of genetic factor. These disorders can be caused by a mutation in a single gene, multiple gene mutations, combined gene mutation and environmental factors, or by chromosome mutation or damage. Gene mutations have been identified as the cause of several disorders including sickle cell anemia, cystic fibrosis, Tay-Sachs disease, Huntington disease, hemophilia, and some cancers.
National Human Genome Research Institute