Most of more than 11 million experimentally established polymorphisms, accumulated in dbSNP, were identified in the intergenic spacers or coding DNA regions. This fact enables interpretation of the former polymorphisms as neutral, while the latter makes clear the biological sense of the associated mutant phenotypes, “the defect of certain proteins”. The association of polymorphisms in regulatory DNA regions with mutant phenotypes is poorly studied. Specifically, the defects in certain DNA/protein binding sites were identified in less than 500 cases. In TATA-containing genes of eukaryotes the TATA box, the TBP (TATA-binding protein) binding site, is located about 30 bp upstream from the transcription start site. Interaction between DNA and TBP triggers assemblage of the preinitiation complex. For 38 TATA box polymorphisms in the genes of commercial and laboratory animals and plants, the effect on TBP-binding activity was evaluated using the equilibrium equation for the four subsequent steps of TBP/TATA box binding (nonspecific binding ↔ sliding ↔ recognition ↔ stabilization). According to the GenBank data, these 38 polymorphisms were associated with the change in a number of selectively valuable traits. Statistically significant congruence of in silico analysis performed with mutant phenotypes (α < 0.05, binomial law) provides suggestion of the mechanism of phenotypic manifestation of these polymorphisms (changing of the TBP-binding activity), as well a validates the possibility of developing the universal test system for experimental-computer prediction of the effects of TATA box mutations in specified genes on selectively valuable traits of the species, varieties, and breeds.
Russian Journal of Genetics – Springer Journals
Published: Apr 25, 2010
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