Candidate SNP Markers of Chronopathologies Are Predicted by a Significant Change in the Affinity of TATA-Binding Protein for Human Gene Promoters

Abstract

Variations in human genome (e.g., single nucleotide polymorphisms, SNPs) may be associated with hereditary diseases, their complications, comorbidities, and drug responses. Using Web service SNP_TATA_Comparator presented in our previous paper, here we analyzed immediate surroundings of known SNP markers of diseases and identified several candidate SNP markers that can significantly change the affinity of TATA-binding protein for human gene promoters, with circadian consequences. For example, rs572527200 may be related to asthma, where symptoms are circadian (worse at night), and rs367732974 may be associated with heart attacks that are characterized by a circadian preference (early morning). By the same method, we analyzed the 90 bp proximal promoter region of each protein-coding transcript of each human gene of the circadian clock core. This analysis yielded 53 candidate SNP markers, such as rs181985043 (susceptibility to acute Q fever in male patients), rs192518038 (higher risk of a heart attack in patients with diabetes), and rs374778785 (emphysema and lung cancer in smokers). If they are properly validated according to clinical standards, these candidate SNP markers may turn out to be useful for physicians (to select optimal treatment for each patient) and for the general population (to choose a lifestyle preventing possible circadian complications of diseases).

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 ].…”

SNP TATA Comparator genomewide landmarks for preventive personalized medicine

“…Using this genomewide landmark, a pregnant woman carrying the minor allele of this SNP and her physician can arrange additional diagnostics to detect the onset and development of this disease during her pregnancy to prevent its fatal outcome. Table 4 contains the results of the Key Words search for circadian rhythm-related comorbidities (170)(171)(172)(173)(174)(175)(176)(177)(178)(179)(180)(181)(182), which are associated with consequences of desynchronoses either among the nervous, immune, digestive, respiratory, and other systems of the human body or between the human body and its environment (109). The most interesting (in our opinion) known SNP marker of myocardial infarction and thrombosis (rs563763767) may indicate that these hereditary diseases have a circadian preference for the early morning (182), which should correspond to the period of the strongest therapeutic effects of the medication used.…”

Candidate SNP markers of social dominance, which may affect the affinity of the TATAbinding protein for human gene promoters

“…таблицу). Более детальное описание метода можно найти в статье , его верификации -в на-ших экспериментах in vivo на куль-турах клеточных линий человека с использованием вектора pGL4.23 (Chadaeva et al, 2016), in vitro в ре-альном времени (Arkova et al, 2014), в неравновесных (Drachkova et al, 2014) и равновесных (Savinkova et al, 2013) условиях, а также на данных независимых экспериментов других авторов (см. обзоры (Ponomarenko et al, 2009Suslov et al, 2010)).…”

“…На основе этой модели мы создали Web-сервис SNP_TATA_Comparator (http://beehive.bionet. nsc.ru/cgi-bin/mgs/tatascan/start.pl) для оценки значимости изменения сродства ТВР к минорному аллелю промотора относительно нормы (анцестральный аллель) и применили его к предсказанию кандидатных SNP-маркеров для ожирения , хронопатологий , аутоиммунных патологий и агрессивности как осложнения при ряде заболеваний (Chadaeva et al, 2016).…”