title: ÐÐ¸Ð¾Ð¸Ð½ÑÐ¾ÑÐ¼Ð°ÑÐ¸ÑÐµÑÐºÐ¸Ðµ Ð¿Ð¾Ð´Ñ Ð¾Ð´Ñ Ðº Ð°Ð½Ð°Ð»Ð¸Ð·Ñ Ð·Ð½Ð°ÑÐ¸Ð¼Ð¾ÑÑÐ¸ Ð²Ð°ÑÐ¸Ð°Ð½ÑÐ¾Ð² Ð½ÑÐºÐ»ÐµÐ¾ÑÐ¸Ð´Ð½Ð¾Ð¹ Ð¿Ð¾ÑÐ»ÐµÐ´Ð¾Ð²Ð°ÑÐµÐ»ÑÐ½Ð¾ÑÑÐ¸, Ð²ÑÑÐ²Ð»ÐµÐ½Ð½ÑÑ Ñ Ð¿Ð°ÑÐ¸ÐµÐ½ÑÐ¾Ð² Ñ Ð½Ð°ÑÐ»ÐµÐ´ÑÑÐ²ÐµÐ½Ð½ÑÐ¼Ð¸ Ð½Ð°ÑÑÑÐµÐ½Ð¸ÑÐ¼Ð¸ ÑÐ¾ÐµÐ´Ð¸Ð½Ð¸ÑÐµÐ»ÑÐ½Ð¾Ð¹ ÑÐºÐ°Ð½Ð¸
title: Ð²ÑÐ¿ÑÑÐºÐ½Ð°Ñ ÐºÐ²Ð°Ð»Ð¸ÑÐ¸ÐºÐ°ÑÐ¸Ð¾Ð½Ð½Ð°Ñ ÑÐ°Ð±Ð¾ÑÐ° Ð±Ð°ÐºÐ°Ð»Ð°Ð²ÑÐ°
titleType: Subtitle
title: Bioinformatic approaches to the analysis of the significance of nucleotide sequence variants revealed in patients with hereditary disorders of connective tissue
Creators: name: ÐÐ¾Ð½Ð¸ÑÐ¸Ð½, ÐÑÐ±Ð¾Ð²Ñ
Publisher: name: Ð¡Ð°Ð½ÐºÑ-ÐÐµÑÐµÑÐ±ÑÑÐ³ÑÐºÐ¸Ð¹ Ð¿Ð¾Ð»Ð¸ÑÐµÑÐ½Ð¸ÑÐµÑÐºÐ¸Ð¹ ÑÐ½Ð¸Ð²ÐµÑÑÐ¸ÑÐµÑ ÐÐµÑÑÐ° ÐÐµÐ»Ð¸ÐºÐ¾Ð³Ð¾
Year: 2020
Subjects: Ð¼ÐµÐ´Ð¸ÑÐ¸Ð½ÑÐºÐ°Ñ Ð³ÐµÐ½ÐµÑÐ¸ÐºÐ°
Ð½Ð°ÑÐ»ÐµÐ´ÑÑÐ²ÐµÐ½Ð½ÑÐµ Ð·Ð°Ð±Ð¾Ð»ÐµÐ²Ð°Ð½Ð¸Ñ ÑÐ¾ÐµÐ´Ð¸Ð½Ð¸ÑÐµÐ»ÑÐ½Ð¾Ð¹ ÑÐºÐ°Ð½Ð¸
Ð±Ð¸Ð¾Ð¸Ð½ÑÐ¾ÑÐ¼Ð°ÑÐ¸ÐºÐ°
ÐºÐ¾Ð»Ð»Ð°Ð³ÐµÐ½
Ð²Ð°ÑÐ¸Ð°Ð½ÑÑ Ð½ÑÐºÐ»ÐµÐ¾ÑÐ¸Ð´Ð½Ð¾Ð¹ Ð¿Ð¾ÑÐ»ÐµÐ´Ð¾Ð²Ð°ÑÐµÐ»ÑÐ½Ð¾ÑÑÐ¸
Ð¿ÑÐµÐ´ÑÐºÐ°Ð·Ð°Ð½Ð¸Ñ Ð¿Ð°ÑÐ¾Ð³ÐµÐ½Ð½Ð¾ÑÑÐ¸
Ð¿ÑÐµÐ´Ð¸ÐºÑÐ¾ÑÑ
medical genetics
hereditary connective tissue diseases
bioinformatics
collagen
nucleotide sequence variants
pathogenicity predictions
predictors

description: ÐÐ°Ð½Ð½Ð°Ñ ÑÐ°Ð±Ð¾ÑÐ° Ð¿Ð¾ÑÐ²ÑÑÐµÐ½Ð° Ð¸Ð·ÑÑÐµÐ½Ð¸Ñ Ð¼Ð¾Ð»ÐµÐºÑÐ»ÑÑÐ½Ð¾-Ð³ÐµÐ½ÐµÑÐ¸ÑÐµÑÐºÐ¸Ñ Ð¿ÑÐ¸ÑÐ¸Ð½ Ð²Ð¾Ð·Ð½Ð¸ÐºÐ½Ð¾Ð²ÐµÐ½Ð¸Ñ ÐºÐ»Ð¸Ð½Ð¸ÑÐµÑÐºÐ¸Ñ Ð¿ÑÐ¾ÑÐ²Ð»ÐµÐ½Ð¸Ð¹ Ð½Ð°ÑÐ»ÐµÐ´ÑÑÐ²ÐµÐ½Ð½Ð¾Ð³Ð¾ Ð½Ð°ÑÑÑÐµÐ½Ð¸Ñ ÑÐ¾ÐµÐ´Ð¸Ð½Ð¸ÑÐµÐ»ÑÐ½Ð¾Ð¹ ÑÐºÐ°Ð½Ð¸ (ÐÐÐ¡Ð¢) Ñ Ð¿Ð°ÑÐ¸ÐµÐ½ÑÐ¾Ð² Ñ Ð¸Ð·ÑÑÐ°ÐµÐ¼ÑÐ¼ ÑÐµÐ½Ð¾ÑÐ¸Ð¿Ð¾Ð¼. ÐÐ»Ñ Ð¸ÑÑÐ»ÐµÐ´Ð¾Ð²Ð°Ð½Ð¸Ñ Ð±ÑÐ»Ð¸ Ð¸ÑÐ¿Ð¾Ð»ÑÐ·Ð¾Ð²Ð°Ð½Ñ Ð¾Ð±ÑÐ°Ð·ÑÑ Ð³ÐµÐ½Ð¾Ð¼Ð½Ð¾Ð¹ ÐÐÐ 42 Ð½ÐµÑÐ¾Ð´ÑÑÐ²ÐµÐ½Ð½ÑÑ Ð¿Ð°ÑÐ¸ÐµÐ½ÑÐ¾Ð² Ñ ÐÐÐ¡Ð¢. ÐÑÐµÐ½ÐºÐ° Ð¿Ð°ÑÐ¾Ð³ÐµÐ½Ð½Ð¾ÑÑÐ¸ Ð²ÑÑÐ²Ð»ÐµÐ½Ð½ÑÑ Ð²Ð°ÑÐ¸Ð°Ð½ÑÐ¾Ð² 1269 Ð³ÐµÐ½Ð¾Ð², ÑÐ²ÑÐ·Ð°Ð½Ð½ÑÑ Ñ ÑÐ°Ð·Ð²Ð¸ÑÐ¸ÐµÐ¼ ÐÐÐ¡Ð¢, Ð±Ð°Ð·Ð¸ÑÐ¾Ð²Ð°Ð»Ð°ÑÑ Ð½Ð° ÑÐµÐºÐ¾Ð¼ÐµÐ½Ð´Ð°ÑÐ¸ÑÑ ACMG Ð¿Ð¾ Ð¸Ð½ÑÐµÑÐ¿ÑÐµÑÐ°ÑÐ¸Ð¸ Ð´Ð°Ð½Ð½ÑÑ, Ð¿Ð¾Ð»ÑÑÐµÐ½Ð½ÑÑ Ð¼ÐµÑÐ¾Ð´Ð¾Ð¼ Ð¿Ð¾Ð»Ð½Ð¾ÑÐºÐ·Ð¾Ð¼Ð½Ð¾Ð³Ð¾ ÑÐµÐºÐ²ÐµÐ½Ð¸ÑÐ¾Ð²Ð°Ð½Ð¸Ñ ÑÐ»ÐµÐ´ÑÑÑÐµÐ³Ð¾ Ð¿Ð¾ÐºÐ¾Ð»ÐµÐ½Ð¸Ñ. Ð ÑÐµÐ·ÑÐ»ÑÑÐ°ÑÐµ Ð¾ÑÐµÐ½ÐºÐ¸ Ð¿Ð°ÑÐ¾Ð³ÐµÐ½Ð½Ð¾ÑÑÐ¸ Ð²ÑÑÐ²Ð»ÐµÐ½Ð¾ 17 Ð¿Ð°ÑÐ¾Ð³ÐµÐ½Ð½ÑÑ ÑÐ»ÐµÐ´ÑÑÑÐ¸Ñ Ð³ÐµÐ½Ð¾Ð²: ANO5, BTD, CNGB3, COL7A1, FIG4, GPR179, HGD, KIAA0586, KRT14, LAMA2, NEB, PNKP, SLC26A2, VPS13B, VWF, WDR35, YARS2 Ð¸ 18 Ð²ÐµÑÐ¾ÑÑÐ½ÑÑ Ð¿Ð°ÑÐ¾Ð³ÐµÐ½Ð½ÑÑ Ð²Ð°ÑÐ¸Ð°Ð½ÑÐ¾Ð² Ð³ÐµÐ½Ð¾Ð²: A2ML1, ADAR, CCDC78, CCDC8, CYP1B1, DEAF1, GCDH, GRM1, IFIH1, NUP107, RAPSN, RYR1, SAMD9, SDHD, SLX4, SPG7, XPA. ÐÐ¾ÑÐ»Ðµ ÑÐ¸ÑÐ»ÐµÐ½Ð½Ð¾Ð³Ð¾ Ð¿ÑÐµÐ´ÑÐºÐ°Ð·Ð°Ð½Ð¸Ñ Ð²Ð»Ð¸ÑÐ½Ð¸Ñ 108 Ð²Ð°ÑÐ¸Ð°Ð½ÑÐ¾Ð² Ð½ÐµÐ¸Ð·Ð²ÐµÑÑÐ½Ð¾Ð¹ ÐºÐ»Ð¸Ð½Ð¸ÑÐµÑÐºÐ¾Ð¹ Ð·Ð½Ð°ÑÐ¸Ð¼Ð¾ÑÑÐ¸ Ð½Ð° ÑÑÐ°Ð±Ð¸Ð»ÑÐ½Ð¾ÑÑÑ Ð±ÐµÐ»ÐºÐ° Ð² Ð²Ð¾Ð·Ð½Ð¸ÐºÐ½Ð¾Ð²ÐµÐ½Ð¸Ð¸ Ð¸ ÑÐ°Ð·Ð²Ð¸ÑÐ¸Ð¸ Ð½Ð°ÑÑÑÐµÐ½Ð¸Ñ ÑÐ¾ÐµÐ´Ð¸Ð½Ð¸ÑÐµÐ»ÑÐ½Ð¾Ð¹ ÑÐºÐ°Ð½Ð¸ Ð²ÑÑÐ²Ð»ÐµÐ½Ñ ÑÐ»ÐµÐ´ÑÑÑÐ¸Ðµ Ð²Ð°ÑÐ¸Ð°Ð½ÑÑ - rs200457046 Ð³ÐµÐ½Ð° SCN9A, rs747448117 Ð³ÐµÐ½Ð° DNMT3A Ð¸ rs772861343 Ð³ÐµÐ½Ð° PLOD1. ÐÐ°Ð½Ð½ÑÐµ, Ð¿Ð¾Ð»ÑÑÐµÐ½Ð½ÑÐµ Ð² ÑÐ¾Ð´Ðµ ÑÐ°Ð±Ð¾ÑÑ, ÑÐºÐ°Ð·ÑÐ²Ð°ÑÑ Ð½Ð° Ð¿Ð¾ÑÐµÐ½ÑÐ¸Ð°Ð»ÑÐ½Ð¾Ðµ Ð²Ð»Ð¸ÑÐ½Ð¸Ðµ Ð²ÑÑÐ²Ð»ÐµÐ½Ð½ÑÑ Ð½Ð°Ð¼Ð¸ Ð²Ð°ÑÐ¸Ð°Ð½ÑÐ¾Ð² Ð½ÑÐºÐ»ÐµÐ¾ÑÐ¸Ð´Ð½Ð¾Ð¹ Ð¿Ð¾ÑÐ»ÐµÐ´Ð¾Ð²Ð°ÑÐµÐ»ÑÐ½Ð¾ÑÑÐ¸ Ð½Ð° ÑÐµÐ½Ð¾ÑÐ¸Ð¿ ÐÐÐ¡Ð¢.
description: The given work is devoted to studying the significance of the revealed variants of nucleotide sequence potentially responsible for the formation of clinical manifestations in patients with hereditary disorders of connective tissue. There has been valuable progress in the use of different molecular diagnostic technologies to clarify the classification of the heritable disorders of connective tissue (HDCT). Nowadays many of them are only based on clinical criteria, due to the absence of an identified gene and a protein, thus the main objective was to identify possible molecular genetic causes of HDCT development. For research, genomic DNA samples of 42 unrelated patients with HDCT were used. Whole-exome sequencing was performed on a HiSeq2500. Assessment of the pathogenicity of the identified variants was based on the recommendations of ACMG on the interpretation of data obtained by the next-generation sequencing method. As a result of the pathogenicity assessment, 17 pathogenic, 18 probably pathogenic variants and 108 variants of unknown clinical significance were identified. After computational prediction of the effect of these mutations on protein stability, 3 VUS variants are considered to be involved in the development of connective tissue - rs200457046, rs747448117 Ð¸ rs772861343. Considering the results of the study, we cannot exclude that the variants and genes we identified may have a pathogenic effect, forming the HDCT phenotype.