Single nucleotide polymorphisms are substitutions in one nucleotide by a different nucleotide in a DNA sequence in a person’s germline. This is the most common type of variation in the eggs or sperm of individuals. These substitutions, also called point mutations, can be passed on to offspring. The substitutions can be found in the coding sequences as well as the non-coding sequences of a person’s genome. Apparently, there could be as many as four to five million SNPs per person.

The impact that these single substitutions have on subsequent offspring has been studied, for example, through Genome Wide Association Studies (GWAS). Now that the full genome is available for scientists to study, computer studies can compare the sequences of large groups of people. One major topic of interest is to find genetic markers for various congenital diseases. If scientists can discover what is defective in a piece of DNA, the hope is that a treatment can be developed for that particular disease. Prior to the Human Genome Project (2003), medical geneticists compared particular relevant genes from affected individuals with those from normal people, a method that was often inconclusive.

Now with the GWAS, scientists could scan the genomes of thousands of people, some affected by a disease and others who are healthy. They were typically looking for SNP markers which showed some kind of statistical association to people with a particular disease. The interesting thing is that the scientists did find associations, or markers, between SNPs and various diseases. The astonishing thing was however that most of these markers have been found in the non-coding DNA (what formerly was considered ‘junk’!)

A series of articles in Nature [Feb. 11, 2021 vol. 590 #7845 pp. 212-215] reflected on the significance of the Human Genome Project. The main story of the 20 years since 2001 concerns how we understand the role of non-coding DNA:  “with the HGP draft in hand, the discovery of non-protein-coding elements exploded.” p. 214. And indeed “The results highlight how the Human Genome Project (HGP), with its comprehensive list of protein-coding genes, spurred a new era of elucidating the function of the non-coding portion of the genome and paved the way for therapeutic developments.”  p. 212

The bottom line is that Single Nucleotide Polymorphisms have been used in Genome Wide Association Studies to discover areas within the non-coding DNA which exert a major impact on the health or lack of health of individuals. If a change in non-coding DNA is connected with a disease condition, it is obvious that it must have an important function. Thus, the use of SNPs has been important in discovering that there is a function to considerable stretches of non-coding DNA.