SINGLE NUCLEOTIDE POLYMORPHISMS (SNPS)

7 Apr

SINGLE NUCLEOTIDE POLYMORPHISMS (SNPS)

Figure 2.6 The structure of a short tandem repeat. The core repeat can be between 1 and 6 bp. This example shows the structure of two alleles from the locus D8S1179. The DNA either side of the core repeats is called flanking DNA. The alleles are named according to the number of repeats that they contain tool for just about every forensic laboratory in the world – the vast majority of forensic genetic casework involves the analysis of STR polymorphisms. There are thousands of STRs that can potentially be used for forensic analysis. STR lociarespreadthroughoutthegenomeincludingthe22autosomalchromosomesandthe X and Y sex chromosomes. They have a core unit of between 1 and 6 bp and the repeats typically range from 50 to 300 bp. The majority of the loci that are used in forensic ge- netics are tetranucleotide repeats, which have a four base pair repeat motif (Figure 2.6). STRs satisfy all the requirements for a forensic marker: they are robust, leading to successful analysis of a wide range of biological material; the results generated in different laboratories are easily compared; they are highly discriminatory, especially when analysing a large number of loci simultaneously (multiplexing); they are very sensitive, requiring only a few cells for a successful analysis; it is relatively cheap and easy to generate STR profiles; and there is a large number of STRs throughout the genome that do not appear to be under any selective pressure.

Single nucleotide polymorphisms (SNPs)
The simplest type of polymorphism is the SNP; single base differences in the sequence of the DNA. The structure of a typical SNP polymorphism is illustrated in Figure 2.7. SNPs are formed when errors (mutations) occur as the cell undergoes DNA repli- cation during meiosis. Some regions of the genome are richer in SNPs than others, for example chromosome 1 contains a SNP on average every 1.45 kb compared with chromosome 19, where SNPs occur on average every 2.18 kb [21]. SNPs normally have just two alleles, for example one allele with a guanine and one with an adenine, and therefore are not highly polymorphic and do not fit with the

Figure 2.7 A single nucleotide polymorphism (SNP). Two alleles are shown that differ at one po- sition, indicated by the star: the fourth position in allele G is a guanine while in allele A it is an adenine. In most cases, the mutation event at the specific locus which creates a SNP is a unique event and only two different alleles (biallelic) are normally found ideal properties of DNA polymorphisms for forensic analysis. However, SNPs are so abundant throughout the genome that it is theoretically possible to type hundreds of them. This will make the combined power of discrimination very high. It is estimated that to achieve the same discriminatory power that is achieved using 10 STRs, 50 – 80 SNPs would have to be analysed [22, 23]. With current technology, this is much more difficult than analysing 10 STR loci. With the exception of the analysis of mitochondrial DNA (see Chapter 13) SNPs have not been used widely in forensic science to date, and the dominance of tandem repeated DNA will continue for the foreseeable future [24]. SNPs are however finding a number of niche applications (see Chapter 12).

Further reading

Brown, T.A. (2007) Genomes 3. Garland Science.

WWW resource
The Human Genome Project Information: a website funded by the U.S. Depart- ment of Energy which along with and the National Institutes of Health coordi- nated the project. Contains resources on all aspects of the Human Genome Project.
http://www.ornl.gov/sci/techresources/ Human Genome/home.shtml

References

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21. Thorisson, G.A., and Stein, L.D. (2003) The SNP Consortium website: past, present and future. Nucleic Acids Research 31, 124-127.
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