Candidate SNP markers of aggressiveness-related complications and comorbidities of genetic diseases are predicted by a significant change in the affinity of TATA-binding protein for human gene promotersReportar como inadecuado




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BMC Genomics

, 17:995

First Online: 28 December 2016DOI: 10.1186-s12864-016-3353-3

Cite this article as: Chadaeva, I.V., Ponomarenko, M.P., Rasskazov, D.A. et al. BMC Genomics 2016 17Suppl 14: 995. doi:10.1186-s12864-016-3353-3

Abstract

BackgroundAggressiveness in humans is a hereditary behavioral trait that mobilizes all systems of the body—first of all, the nervous and endocrine systems, and then the respiratory, vascular, muscular, and others—e.g., for the defense of oneself, children, family, shelter, territory, and other possessions as well as personal interests. The level of aggressiveness of a person determines many other characteristics of quality of life and lifespan, acting as a stress factor. Aggressive behavior depends on many parameters such as age, gender, diseases and treatment, diet, and environmental conditions. Among them, genetic factors are believed to be the main parameters that are well-studied at the factual level, but in actuality, genome-wide studies of aggressive behavior appeared relatively recently. One of the biggest projects of the modern science—1000 Genomes—involves identification of single nucleotide polymorphisms SNPs, i.e., differences of individual genomes from the reference genome. SNPs can be associated with hereditary diseases, their complications, comorbidities, and responses to stress or a drug. Clinical comparisons between cohorts of patients and healthy volunteers as a control allow for identifying SNPs whose allele frequencies significantly separate them from one another as markers of the above conditions. Computer-based preliminary analysis of millions of SNPs detected by the 1000 Genomes project can accelerate clinical search for SNP markers due to preliminary whole-genome search for the most meaningful candidate SNP markers and discarding of neutral and poorly substantiated SNPs.

ResultsHere, we combine two computer-based search methods for SNPs that alter gene expression {i} Web service SNP TATA Comparator DNA sequence analysis and {ii} PubMed-based manual search for articles on aggressiveness using heuristic keywords. Near the known binding sites for TATA-binding protein TBP in human gene promoters, we found aggressiveness-related candidate SNP markers, including rs1143627 associated with higher aggressiveness in patients undergoing cytokine immunotherapy, rs544850971 higher aggressiveness in old women taking lipid-lowering medication, and rs10895068 childhood aggressiveness-related obesity in adolescence with cardiovascular complications in adulthood.

ConclusionsAfter validation of these candidate markers by clinical protocols, these SNPs may become useful for physicians may help to improve treatment of patients and for the general population a lifestyle choice preventing aggressiveness-related complications.

KeywordsAggressiveness Gene Promoter TATA-binding protein Single nucleotide polymorphism Candidate SNP marker Keyword-based search Prediction in silico AbbreviationsALSAmyotrophic lateral sclerosis

EMSAElectrophoretic mobility shift assay

KdEquilibrium dissociation constant

lnNatural logarithm

mutMinor allele of SNPs

SNPSingle nucleotide polymorphism

TBPTATA-binding protein

TFTranscription factor

TSSTranscription start site

WTWild type norm

Electronic supplementary materialThe online version of this article doi:10.1186-s12864-016-3353-3 contains supplementary material, which is available to authorized users.

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Autor: Irina V. Chadaeva - Mikhail P. Ponomarenko - Dmitry A. Rasskazov - Ekaterina B. Sharypova - Elena V. Kashina - Marina Y

Fuente: https://link.springer.com/







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