| Genetic Variation Within Species and SNPs |
A polymorphism, the existence of two or more forms of sequence between different individuals of the same species, can arise from a change in a single nucleotide. These single nucleotide polymorphisms (SNPs) account for ninety percent of all polymorphisms in humans. The number of SNPs between two genomes provides a measure of sequence variation; however, the variation is not uniform over the genome. About two-thirds of SNPs are in noncoding DNA and tend to be concentrated in certain locations in the chromosome. In addition, sex chromsomes have a lower concentration of SNPs than autosomes.
There are about three million SNPs in the human genome, or about 1 per 1000 nucleotides. SNPs are ideal genetic markers for many applications because they are stable, widespread, and can often be linked to particular characteristics (phenotypes) of interest. They are proving to be among the most useful human markers for studies of evolutionary genetics and medicine.
Not all SNPs, even when they are present in coding genes, lead to visible or phenotypic differences among individuals. Changes in the DNA sequence don't always change the amino acid sequence of the protein. For example, a change from GGG to GGC results in no change in the protein because both codons result in a glycine in the protein. This is called a synonymous mutation or silent mutation; non-synonymous substitutions do cause a change in the amino acid. About half of all SNPs in genes are non-synonymous and therefore can account for diversity between individuals or populations. Depending on the particular change in an amino acid caused by a nonsynonymous mutation, the resulting protein may be an active, inactive, or partially active. It may also be active in a different way.
One well-characterized SNP exists in a gene in chromosome 6. Individuals with cysteine at amino acid position 282 are healthy; however, about 1 in 200-400 Caucasians of Northern European descent possess two copies of that gene where the amino acid is tyrosine instead of cysteine. Due to this one change, these individuals have a disease called hereditary hemochromatosis. People afflicted with this disease accumulate high levels of iron, which causes permanent damage to the organs, especially the liver. About ten percent of these individuals carry only one copy of this mutation; they are heterozygous and are carriers of the disease. A genetic test for hereditary hemochromatosis is available, which can detect the SNP. If the disease is found, medical professionals can then determine whether the person is homozygous or heterozygous for this allele. Another example of a single SNP that has a dramatic effect is the one that leads to sickle cell anemia. (See the Human Evolution unit.)