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 promoters

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

A Rat Model of Human Behavior Provides Evidence of Natural Selection Against Underexpression of Aggressiveness-Related Genes in Humans

“…Earlier, we created Web service SNP_TATA_Comparator 1 for genome-wide SNP analysis (Ponomarenko et al, 2015). Using it, we predicted candidate SNP markers of human aggressiveness (Chadaeva et al, 2016) and natural selection against underexpression of human aggressiveness-related genes (Chadaeva et al, 2017). Recently, we proved this natural selection pattern using F1 hybrid male mice as an animal model of human heredity (Chadaeva et al, 2019).…”

Candidate SNP markers of reproductive potential are predicted by a significant change in the affinity of TATA-binding protein for human gene promoters

“…In our previous studies, we developed public Web service SNP_TATA_Comparator ( http://beehive.bionet.nsc.ru/cgi-bin/mgs/tatascan/start.pl ) [ 53 ] and applied it to predict candidate SNP markers within TATA boxes of human genes associated with obesity [ 54 ], autoimmune diseases [ 55 ], chronopathology [ 56 ], aggressiveness [ 57 , 58 ], Alzheimer’s disease [ 59 ], and efficacy of anticancer chemotherapy [ 60 ] (for review, see [ 20 ]). In the present work, we applied our Web service [ 53 ] in the same way to human reproductive potential as the most common concept of population ecology dealing with the evolutionary success of either individuals [ 2 ] or populations [ 3 ].…”

Candidate SNP-markers altering TBP binding affinity for promoters of the Y-linked genes CDY2A, SHOX, and ZFY are lowering many indexes of reproductive potential in men

“…Ранее мы создали Webсервисы SNP_TATA_Comparator (Ponomarenko M. et al, 2015) и SNP_TATA_Ztester (Sharypova et al, 2018) для оценки статистической значимости влияния SNP на сродство ТВР к промоторам генов человека и других эукариот с использованием библиотеки BioPerl (Stajich et al, 2002), доступа к базе данных En sembl (Cunningham et al, 2019) и с помощью других источников данных соответственно. На этой методической основе мы предсказали кандидатные SNPмаркеры ожирения (Ar kova et al, 2015), агрессивности (Chadaeva et al, 2016), нарушений циркадного ритма , атеросклероза (Ponomarenko M. et al, 2019), аутоиммунных заболеваний , болезни Альцгеймера , резистентности к противоопухолевой химиотерапии (Turnaev et al, 2016), предрасположенности к социальному доминированию и подчинению у людей (Chadaeva et al, 2019).…”