Cancer News Information

With the determination of the base sequence of the human genome, research is turning more towards genetic variation. Every normal human genome is unique in that no two people are exactly alike. Genetic variation also includes incidental changes that result in mutation or genetic mistakes. The mutation of a single base may have no effect on the protein product of an expressed gene. However, a single mutation can lead to the production of a protein completely different from the necessary protein. These mutations can have detrimental results.

Single Base Changes in the Gene: Substitution

The human genome consists of 3 billion repeating bases designated as A, G, C or T. The combination of 3 bases, a codon, determines what amino acid that will be added to a protein chain. This calculates to a total of 64 possible 3 base combinations that represent the 20 amino acids forming a protein molecule. Therefore, certain amino acids are represented by more than one codon. One example of an amino acid is Serine. The codes for Serine include TCT, TCC, TCA, and TCG. A mutation in the third base of the codon for Serine does not effect the formulation of the protein. It should be noted that Serine is also coded with AGT and AGC. Mutation that results in the third base to A or G would change the amino acid expressed by the gene to Arginine. This may or may not affect the protein.

Mutations are not Limited to Substitution

Mutations that can have more profound effects on gene expression are the result of the insertion or deletion of single or multiple bases. This is called an indel, which stands for insertion-deletion. The effects of an indel cause change by shifting the entire code of the gene, also known as a frameshift, resulting in the formation of a completely different protein. An example of this is an indel's affect on the DNA sequence TTC-CCC-AGC-GAC. This codes the four amino acids Phenaline-Proline-Serine-Asperine. If one base is deleted from the DNA code giving TCC-CCA-GCG-ACX, then the amino acids coded are Serine-Proline-Alanine-Thromine. The resulting protein may provide no useful function.

Examples of Genetic Diseases Caused by Mutation

Tay-Sach's disease is a well-documented disorder caused by a base deletion in the gene coding for hexosaminidase. This enzyme is important for removal of certain toxic chemicals that can build up in the brain. Tay-Sach's causes mental and physical impairment and can be fatal. An insertion in chromosome 15 causes a frameshift in the hexosaminidase gene.

Crohn's Disease is caused by the addition of a cystosine base along chromosome 16. The addition of this base does not completely eliminate the function of the enzyme product. However, it does reduce overall activity, thus leading to inflammatory bowel disease.

There are a number of well-known methods researchers use to detect mutations in genetic materials. Quite often it is a matter of comparing an unknown sample with a wild type to locate base differences. Automated Sanger sequencing is used to identify single base polymorphisms or SNPs. A sample is isolated from genomic DNA and amplified by the Polymerase Chain Reaction to produce useable copies of a particular region of the genome. Humans and other species are hereozygous so they contain two copies of each gene. A mutation in one copy would be detected as a hereozygote where two bases occupy the same position in the sample.

Mutations do not necessarily cause negative effects in gene function. Mutation has been one of the driving forces behind evolution. An alternative trait resulting from genetic differences could lead to an improved characteristic that increases survival capability.