Genetic Variants in Transcription Factor Binding Sites in Humans: Triggered by Natural Selection and Triggers of Diseases

Abstract

Variants of transcription factor binding sites (TFBSs) constitute an important part of the human genome. Current evidence demonstrates close links between nucleotides within TFBSs and gene expression. There are multiple pathways through which genomic sequences located in TFBSs regulate gene expression, and recent genome-wide association studies have shown the biological significance of TFBS variation in human phenotypes. However, numerous challenges remain in the study of TFBS polymorphisms. This article aims to cover the current state of understanding as regards the genomic features of TFBSs and TFBS variants; the mechanisms through which TFBS variants regulate gene expression; the approaches to studying the effects of nucleotide changes that create or disrupt TFBSs; the challenges faced in studies of TFBS sequence variations; the effects of natural selection on collections of TFBSs; in addition to the insights gained from the study of TFBS alleles related to gout, its associated comorbidities (increased body mass index, chronic kidney disease, diabetes, dyslipidemia, coronary artery disease, ischemic heart disease, hypertension, hyperuricemia, osteoporosis, and prostate cancer), and the treatment responses of patients.

Chromatin accessibility associated with aquaculture relevant traits in tilapia

“…This is supported by the fact that nearly all (99%) accessible gene promoter regions have a SNP with most (90%) being a rare variant. Gene promoter regions are enriched for TFBSs 7 , as are accessible regions 47,48 , and thus, variation, including rare variation 49 , at TFBSs is a major target of genetic selection 50 and a key contributor to adaptive phenotypes 6,7,51 . Using TFBSs in accessible gene promoter regions, we identified a total of 3,398,768 transcription factor (TF) – target gene (TG) relationships in Nile tilapia.…”

Polymorphisms within DIO2 and GADD45A genes increase the risk of liver disease progression in chronic hepatitis b carriers

“…Apart from the well-known risk factors such as older age, male gender, chronic active hepatitis, higher ALT levels, or history of decompensation, accumulation of genetic alteration during progression from health, through fibrosis to HCC are now considered of great importance 17 . In this study, we have focused on genetic polymorphism within transcription factor binding sites which are recently suggested as important players in downstream gene expression and phenotypic variations predisposing to different disease development 18 . We have performed an extensive literature review for candidate SNPs located at TFBSs identified by GWAS contributing to complex disease risk.…”

Practical application of massively parallel reporter assay in biotechnology and medicine

“…Методы полногеномного поиска ассоциаций (GWAS) позволяют идентифицировать геномные полиморфизмы, ассоциированные с различными патологиями [148][149][150][151]. Высокая частота встречаемости клинически значимых полиморфизмов в ЦРЭ позволяет предположить их влияние на регуляцию генов, задействованных в патогенезе заболевания [152]. Исследование транскриптома и GWAS-анализ позволяют предсказывать геномные локусы количественных признаков экспрессии (eQTL), ассоциированные с изменением уровня активности ОБЗОРЫ https://doi.org/10.17816/clinpract115063 генов [153].…”