Single Nucleotide Polymorphisms (SNPs) consist of single nucleotide substitutions at specific loci within the genome. SNPs may pinpoint susceptibility to disease as illustrated by the non-synonymous and non-conservative mutation found in the Sickle Cell trait. Most SNPs occur outside of coding sequences where there is reduced selective pressure, however these SNPs may also modify the expression of genes. While many SNPs do not correspond directly with traits in obvious ways, they are useful markers that are associated with inheritance through genetic linkage.
When SNPs occur within coding regions they are termed synonymous (resulting in same amino acid coded) or non-synonymous (resulting in a change in the coded amino acid). Nonsense mutations result in premature stop codons that terminate the coding sequence while missense mutations result in a different amino acid at the location. Missense mutations may be characterized as conservative if the variant amino acid shares biochemical characteristics with the original or non-conservative if the variant is dissimilar.
While Charles Darwin is know for describing a mechanism for evolution in his The Origin of Species by Means of Natural Selection, he also mused about a domestication syndrome in
The Variation of Animals and Plants under Domestication. Domestication syndrome describes refers to two sets of changed phenotypic traits common across many domesticated organisms that may have arisen from the artificial selection process. While these traits were not primarily the ones of interest in the domestication process, there is a trend across different companion animals and livestock to share these traits. This demonstrates a genetic linkage of the desired trait to these other traits. Some physical traits found in common of domestic animals are floppy ears, shorter snouts, spots or lower pigmentation associated with their intended tameness. No matter what the phenotype may be, these characteristics illustrate a number of different alleles that have been collected through the inheritance of SNPs. SNPs that result in distinct phenotypes is the basis of tracking genetic linkage of genes in domesticated animals as well as humans that can offer insight into familial lineages within organisms.
Student Handouts from HHMI Biointeractive
Amplified Polymorphic Sequences
PCR can be used to amplify polymorphic regions. The revelation of polymorphism in these amplified sequences can be illustrated as mini/microsatellites or VNTRs/STRs where variations in length demonstrate differences in repeated elements in what can be described as Amplified Fragment Length Polymorphisms (AFLPs). Cleaved Amplified Polymorphic Sequences (CAPS) represent PCR of loci known to contain polymorphic restriction sites. Different alleles using CAPS may be revealed by the presence or absence of RE digestion of amplified products that result in differential banding patterns. In these cases, SNPs may have historically introduced or ablated the presence of a specific restriction site and permits for the presentation of different alleles. A modification of CAPS specifically uses long primers that intentionally introduce a restriction site where one does not exist based on SNPs within the amplified region for SNPs not naturally creating a restriction site. The intentional creation or removal of restrictions sites for one allele versus the other in this case is referred to as a derived Cleaved Amplified Polymorphic Sequence (dCAPS).
dCAPS has the advantage of studying alleles using AFLPs technology through incorporation of a digestion site for genotyping purposes. A great disadvantage of this system is the mismatches in the primers lowers the PCR specificity. Design of dCAPS primers for SNP identification can be done at http://helix.wustl.edu/dcaps/dcaps.html
An example of dCAPS is the PTC lab exercise.