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SNP array

Thursday 18 March 2004

A SNP array is a type of DNA microarray which is used to detect single nucleotide polymorphisms (SNPs) within a population.

A single nucleotide polymorphism (SNP) is a variation at a single site in DNA. It is the most frequent variation in the genome and there are about 5-10 million SNPs in the human genome.

As SNPs are highly conserved throughout evolution and within population, the map of SNPs serves as an excellent genotypic marker for research.

Principles

The basic principles of SNP-array is the same as the DNA microarray which is the convergence of DNA hybridization, fluorescence microscopy and solid surface DNA capture. The three mandatory components of the SNP arrays are

1. the array that contains immobilized nucleic acid sequences or target;
2. one or more labeled probes;
3. a detection system that records and interprets the hybridization signal.

To achieve relative concentration independence and minimal cross-hybridization, raw sequences and SNPs of multiple databases are scanned to design the probes.

Each SNP on the array is interrogated with different probes. Depending on the purpose of experiments, the amount of SNPs present on an array is considered.

Applications

An SNP array is a useful tool to study the whole genome. The most important application of SNP array is in determining disease susceptibility and consequently, in pharmacogenomics by measuring the efficacy of drug therapies specifically for the individual.

As each individual has many single nucleotide polymorphisms that together create a unique DNA sequence, SNP-based linkage analysis could be performed to map disease loci, and hence determine disease susceptibility genes for an individual.

The combination of SNP maps and high density SNP array allows the use of SNPs as the markers for Mendelian diseases with complex traits efficiently.

For example, whole-genome genetic linkage analysis shows significant linkage for many diseases such as rheumatoid arthritis, a common chronic inflammatory disease, prostate cancer, neonatal diabetes. As a result, drugs can be personally designed to efficiently act on a group of individuals or even each individual.

In oncogenetics, SNP-array can be used for studying the loss of heterozygosity. Loss of heterozygosity (LOH) is a form of allelic imbalance that can result from the complete loss of an allele or from an increase in copy number of one allele relative to the other.

Using high density SNP array to detect LOH allows identification of pattern of allelic imbalance with potential prognostic and diagnostic utilities.

This usage of SNP array has a huge potential in cancer diagnostics as LOH is a prominent characteristic of most human cancers.

Palteforms

- Genome-Wide Human SNP Array 6.0 (Link) by Affymetrix

References

- Wikipedia

- Sheils, O., Finn, S. and O’Leary J., 2003. Nucleic acid microarray: an overview, Current diagnostic pathology; 9:155-158

- Sellick GS, Longman C, Tolmie J, Newbury-Ecob R, Geenhalgh L, Hughes S, Whiteford M, Garrett C, Houlston RS., 2004, Genome-wide linkage searches for Mendelian disease loci can be efficiently conducted using high-density SNP genotyping arrays, Nucleic Acids Res. 32 (20):e164, 2004

- John, S., Shephard, N., Liu, G., Zeggini, E., Cao, M., Chen, W., Vasavda, N., Mills, T., Barton, A., Hinks, A., Eyre, S., Johes, K.W., Ollier, W., Silman, A., Gibson, N., Worthington, J., and Kennedy, G.C., 2004. Whole-Genome scan, in a complex disease, using 11,245 single-nucleotide polymorphism: comparison with microsatellites, Am. J. Hum. Genet. 75:54-64

- Schaid, D.J., Guenther, J.C., Christensen, G.B., Hebbring, S., Rosenow, C., Hilker, C.A., McDonnell, S.K., Cunningham, J.M., Slager, S.L., Blute, M.L., and Thibodeau, S.N., 2004. Comparison of Microsatellites Versus Single Nucleotide Polymorphisms by a Genome Linkage Screen for Prostate Cancer Susceptibility Loci, American Journal of Human Genetics 75 (6): 948-65

- Mei, R., Galipeau, P.C., Prass, C., Berno, A., Ghandour, G., Patil, N., Wolff, R.K., Chee, M.S., Reid, B.J., and Lockhart, D.J., 2000. Genome-wide detection of allelic imbalance using human SNPs and high-density DNA arrays, Genome Res. 10:1126-1137.

Exemples

- GeneChip Mapping EA 10K Array (Affymetrix)

References

- AssiĆ© G, LaFramboise T, Platzer P, Bertherat J, Stratakis CA, Eng C. SNP arrays in heterogeneous tissue: highly accurate collection of both germline and somatic genetic information from unpaired single tumor samples. Am J Hum Genet. 2008 Apr;82(4):903-15. PMID: 18355774
- Ho SM, Lau KM. DNA microarrays in prostate cancer. Curr Urol Rep. 2002 Feb;3(1):53-60. PMID: 12084220