Widespread genetic heterogeneity of human ribosomal RNA genes.
Widespread genetic heterogeneity of human ribosomal RNA genes.
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DOI：
10.1261/rna.078925.121
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发表时间：
2022-04
期刊：
影响因子：
--
通讯作者：
Laiho M
中科院分区：
文献类型：
--
作者：
Fan W;Eklund E;Sherman RM;Liu H;Pitts S;Ford B;Rajeshkumar NV;Laiho M
多态可以在压力下促进生存，并提供适应性。核糖体RNA(RRNA)基因的遗传多态性来源于该多拷贝基因的内部重复变异和个体间变异。已经提出了相当数量的rRNA序列异质性，但由于缺乏准确的参考序列，估计一直是具有挑战性的。我们在21号染色体(GRCh38)上发现了四个rDNA拷贝，与最近引入的参考序列KY962518.1有99%的相似性。我们使用四个总长145kb的rDNA基因座定制了一条GATK生物信息学管道，用于变量调用，并使用1000基因组计划的高覆盖率全基因组测序(WGS)数据来分析26个种群的2504个个体的变量。我们总共确定了3791个变异位置。变异体非随机定位在rRNA基因上。不变区包括启动子、早期5‘ETS、大部分18S、5.8S、ITS1和大范围的基因内间隔区。在28S rRNA上共观察到470个变异位点。大多数28S rRNA变体位于高度灵活的人类扩展的rRNA螺旋折叠ES7L和ES27L上，这表明这些突变代表了多样性的位置，并可能处于不断进化中。基于RNA-SEQ分析验证了几个变异体。群体分析表明，5‘ETS、ITS2和28S区存在显著的遗传变异，并存在高外显性和频繁变异，这些变异按大陆群体进行分离。这些发现提供了rRNA基因阵列异质性的遗传学观点，并提高了从功能上评估28S rRNA变体如何影响核糖体功能的需要。
Polymorphism drives survival under stress and provides adaptability. Genetic polymorphism of ribosomal RNA (rRNA) genes derives from internal repeat variation of this multicopy gene, and from interindividual variation. A considerable amount of rRNA sequence heterogeneity has been proposed but has been challenging to estimate given the scarcity of accurate reference sequences. We identified four rDNA copies on chromosome 21 (GRCh38) with 99% similarity to recently introduced reference sequence KY962518.1. We customized a GATK bioinformatics pipeline using the four rDNA loci, spanning a total 145 kb, for variant calling and used high-coverage whole-genome sequencing (WGS) data from the 1000 Genomes Project to analyze variants in 2504 individuals from 26 populations. We identified a total of 3791 variant positions. The variants positioned nonrandomly on the rRNA gene. Invariant regions included the promoter, early 5′ ETS, most of 18S, 5.8S, ITS1, and large areas of the intragenic spacer. A total of 470 variant positions were observed on 28S rRNA. The majority of the 28S rRNA variants were located on highly flexible human-expanded rRNA helical folds ES7L and ES27L, suggesting that these represent positions of diversity and are potentially under continuous evolution. Several variants were validated based on RNA-seq analyses. Population analyses showed remarkable ancestry-linked genetic variance and the presence of both high penetrance and frequent variants in the 5′ ETS, ITS2, and 28S regions segregating according to the continental populations. These findings provide a genetic view of rRNA gene array heterogeneity and raise the need to functionally assess how the 28S rRNA variants affect ribosome functions.
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影响因子：
7.3
作者：
Henras, Anthony K.;Plisson-Chastang, Celia;O'Donohue, Marie-Francoise;Chakraborty, Anirban;Gleizes, Pierre-Emmanuel
通讯作者：
Gleizes, Pierre-Emmanuel
DOI：
10.1126/science.aaf7040
发表时间：
2016-07-29
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Holland ML;Lowe R;Caton PW;Gemma C;Carbajosa G;Danson AF;Carpenter AA;Loche E;Ozanne SE;Rakyan VK
通讯作者：
Rakyan VK
影响因子：
3.7
作者：
Kendig, Katherine, I;Baheti, Saurabh;Mainzer, Liudmila S.
通讯作者：
Mainzer, Liudmila S.
影响因子：
64.8
作者：
Ghandi, Mahmoud;Huang, Franklin W.;Sellers, William R.
通讯作者：
Sellers, William R.
影响因子：
10.7
作者：
Escobar, Juan S.;Glemin, Sylvain;Galtier, Nicolas
通讯作者：
Galtier, Nicolas