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Flanking monomer repeats determine decreased context complexity of single nucleotide polymorphism sites in the human genome

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Russian Journal of Genetics: Applied Research

Abstract

The study of the dependence of the mutation frequency in human genome was conducted by the example of a set of documented single nucleotide polymorphisms (SNPs) from the 1000 genomes project. The tasks of the development of new computer methods for the statistical analysis of genetic texts based on estimations of sequences complexity were considered. The application of the complexity profiles in a sliding window to the analysis of sites containing single nucleotide polymorphisms in the human genome was demonstrated. A local decrease in the text complexity near SNPs was established. Based on the analysis of the complexity profiles in the regions containing SNPs, it was demonstrated that the flanking monomer repeats determine the decreased context complexity of single nucleotide polymorphism sites in human genome. The effect of local decrease in the text complexity level for sequences flanking SNP sites was confirmed for the data on polymorphisms in the rat and mouse genomes. Differences in the context organization for coding and regulatory sequences (that are reflected in the text complexity of nucleotide sequences containing SNPs) were determined. Changes in the point mutation frequencies were previously demonstrated for the sequences containing microsatellites. Using more general mathematical apparatus and more complete data, a saturation of local genomic surroundings containing SNPs with polytracts and simple repeated sequences was demonstrated in this work. Oligonucleotides with increased frequency in the genomic SNP surroundings in human were determined; their association with polytracts was demonstrated. The presence of polytracts can indicate a greater probability of a break in the double DNA strand at this point (resulting in an increased frequency of nucleotide substitutions). The obtained estimations were determined by a previously developed complex of computer programs, which allows us to efficiently determine the frequency spectrum of oligonucleotides with a fixed length, to compare nucleotide frequencies in a larger sample (in addition to estimating the complexity of the phased sequences).

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Authors and Affiliations

  1. Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Novosibirsk, Russia

    N. S. Safronova, M. P. Ponomarenko, G. V. Orlova, I. V. Chadaeva & Y. L. Orlov

  2. Novosibirsk State University, Novosibirsk, Russia

    N. S. Safronova, M. P. Ponomarenko & Y. L. Orlov

  3. Sanger Center, Cambridge, UK

    I. I. Abnizova

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  1. N. S. Safronova
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  2. M. P. Ponomarenko
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  3. I. I. Abnizova
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  4. G. V. Orlova
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  5. I. V. Chadaeva
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  6. Y. L. Orlov
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Correspondence to N. S. Safronova.

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Original Russian Text © N.S. Safronova, M.P. Ponomarenko, I.I. Abnizova, G.V. Orlova, I.V. Chadaeva, Y.L. Orlov, 2015, published in Vavilovskii Zhurnal Genetiki i Selektsii, 2015, Vol. 19, No. 6, pp. 668–674.

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Safronova, N.S., Ponomarenko, M.P., Abnizova, I.I. et al. Flanking monomer repeats determine decreased context complexity of single nucleotide polymorphism sites in the human genome. Russ J Genet Appl Res 6, 809–815 (2016). https://doi.org/10.1134/S2079059716070121

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