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SNP arrayIn molecular biology and bioinformatics, a SNP array is a type of DNA microarray which is used to detect polymorphisms within a population. A single nucleotide polymorphism (SNP), a variation at a single site in DNA, is the most frequent type of variation in the genome. For example, there are an estimated 5-10 million SNPs in the human genome. As SNPs are highly conserved throughout evolution and within a population, the map of SNPs serves as an excellent genotypic marker for research. Additional recommended knowledgePrinciplesThe basic principles of SNP array are the same as the DNA microarray. These are the convergence of DNA hybridization, fluorescence microscopy, and solid surface DNA capture. The three mandatory components of the SNP arrays are:
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. ApplicationsAn 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 genetic 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, prostate cancer, and neonatal diabetes. As a result, drugs can be personally designed to efficiently act on a group of individuals who share a common allele - or even a single individual. In addition, SNP array can be used for studying the Loss of heterozygosity (LOH). 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. While other chip-based methods (e.g. Comparative genomic hybridization can detect only genomic gains or deletions), SNP array has the additional advantage of detecting copy number neutral LOH due to uniparental disomy (UPD). In UPD, one allele or whole chromosome from one parent are missing leading to reduplication of the other parental allele (uni-parental = from one parent, disomy = duplicated). In a disease setting this occurrence may be pathologic when the wildtype allelle (e.g. from the mother) is missing and instead two copies of the heterozygous allelle (e.g. from the father) are present. 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. Recent studies based on the SNP array technology have shown that not only solid tumors (e.g. gastric cancer, liver cancer etc) but also hematologic malignancies (ALL, MDS, CML etc) have a high rate of LOH due to genomic deletions or UPD and genomic gains. The results of these studies may help to gain insights into mechanisms of these diseases and to create targeted drugs. References
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This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "SNP_array". A list of authors is available in Wikipedia. |