Polymorphisms single nucleotide repeats

Ethnic variation in allele frequencies can lead to important differences in disease susceptibility, outcome and drug metabolism [68, 69]. In addition to single nucleotide polymorphisms, variable number of tandem repeat (VNTR) regions have been shown to have functional significance. 

Biomolecular MS and in particular MALDI-TOF-MS (see Sections 2.1.22 and 2.2.1) permit the routine analysis of oligonucleotides up to 70-mers, intact nucleic acids, and the direct detection of DNA products with no primer labels with an increase in analysis speed and mass accuracy especially in contrast to traditional DNA separation techniques such as slab gels or capillary electrophoresis. Applications focus on the characterization of single nucleotide polymorphisms (SNPs) and short tandem repeats (STRs). Precise and accurate gene expression measurements show relative and absolute numbers of target molecules determined independently of the number of PCR cycles. DNA methylation can be studied quantitatively. 

Fig. 3. Polymorphisms in the TS gene. Abbreviations.- TSER (thymidylate synthase enhancer region) 2R (two-tandem repeats) 3R (three-tandem repeats) TSER 3G (single nucleotide polymorphism of TSER 3R) -6bp (TS 3 -UTR 6bp deletion polymorphism). (Adapted to Marsh et al. Thymidylate synthase pharmacogenetics. Invest New Drugs 2005).

In a recent study, Mandola et al. showed that the 28 bp TSER tandem repeats contain elements that bind upstream stimulating factor (USF), and also that ligand binding by USF-1 and USF-2 enhances the transcriptional activity of the TS gene (Fig. 2) (42). Electrophoretic mobility shift analysis has shown that the presence of a G-to-C single nucleotide polymorphism (SNP) within the second repeat of the 3R allele leads to decreased ability of upstream stimulatory factor (USF) to bind within the repeat and therefore sequentially result in decreased transcriptional activity of the 3R TS gene variant (42). 

Kawakami K, Watanabe G. Identification and functional analysis of single nucleotide polymorphism in the tandem repeat sequence of thymidylate synthase gene. Cancer Res 2003 63 6004-6007. 

Mareuello E, Altes A, del Rio E et al. Single nucleotide polymorphism in the 5 tandem repeat sequences of thymidylate synthase gene predicts for response to fluorouracil-based chemotherapy in advanced colorectal cancer patients. Int J Cancer 2004 112 733-737. 

Single Nucleotide Polymorphism Database (dbSNP) of Nucleotide Sequence Variation. URL http //www.ncbi.nlm. nih.gov/SNP/index.html. Uses SNP in the much looser sense of minor genetic variations and includes microsatellite repeats and small insertion/deletion polymorphisms. 

Single nucleotide polymorphisms Tryptophan hydroxylase Variable number tandem repeat... 

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