ADGR: Admixture-Informed Differential Gene Regulation.
ADGR: Admixture-Informed Differential Gene Regulation.
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DOI：
10.3390/genes14010147
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发表时间：
2023-01-05
期刊：
影响因子：
3.5
通讯作者：
Kong, Sek Won
中科院分区：
文献类型：
--
作者：
Lee, In-Hee;Kong, Sek Won
基因近端和远端的调控元件参与了基因表达的调控。内含子和基因间隔区的风险等位基因可能通过改变参与基因表达调控的各种DNA结合蛋白的结合亲和力和稳定性来改变基因表达。通过使用来自基因类型-组织表达项目的成对的全基因组序列和组织范围的转录组数据集，我们关注编码和调节区的局部祖先结构，我们调查了总体上遗传变异对组织特异性基因表达调控的影响。使用RFMix和1000基因组计划的参考小组确定编码区、直接和远端上游区以及远端调控区的本地祖先起源。对于每个组织，基因表达水平的个体间差异被估计为编码区域和调控区域之间的一致或不一致的本地祖先所解释的。与欧洲人相比，非洲人后裔在当地祖先结构上表现出更频繁的变化，单倍型块更短。腺苷脱氨酶样基因(Adal)的表达水平与多种组织类型调节区的混合祖先结构显著相关。需要进一步的验证才能了解调节区的本地祖先结构对人类和其他物种基因表达调节的影响。
The regulatory elements in proximal and distal regions of genes are involved in the regulation of gene expression. Risk alleles in intronic and intergenic regions may alter gene expression by modifying the binding affinity and stability of diverse DNA-binding proteins implicated in gene expression regulation. By focusing on the local ancestral structure of coding and regulatory regions using the paired whole-genome sequence and tissue-wide transcriptome datasets from the Genotype-Tissue Expression project, we investigated the impact of genetic variants, in aggregate, on tissue-specific gene expression regulation. Local ancestral origins of the coding region, immediate and distant upstream regions, and distal regulatory region were determined using RFMix with the reference panel from the 1000 Genomes Project. For each tissue, inter-individual variation of gene expression levels explained by concordant or discordant local ancestry between coding and regulatory regions was estimated. Compared to European, African descent showed more frequent change in local ancestral structure, with shorter haplotype blocks. The expression level of the Adenosine Deaminase Like (ADAL) gene was significantly associated with admixed ancestral structure in the regulatory region across multiple tissue types. Further validations are required to understand the impact of the local ancestral structure of regulatory regions on gene expression regulation in humans and other species.
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影响因子：
64.8
作者：
通讯作者：
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影响因子：
14.9
作者：
Frankish A;Diekhans M;Ferreira AM;Johnson R;Jungreis I;Loveland J;Mudge JM;Sisu C;Wright J;Armstrong J;Barnes I;Berry A;Bignell A;Carbonell Sala S;Chrast J;Cunningham F;Di Domenico T;Donaldson S;Fiddes IT;García Girón C;Gonzalez JM;Grego T;Hardy M;Hourlier T;Hunt T;Izuogu OG;Lagarde J;Martin FJ;Martínez L;Mohanan S;Muir P;Navarro FCP;Parker A;Pei B;Pozo F;Ruffier M;Schmitt BM;Stapleton E;Suner MM;Sycheva I;Uszczynska-Ratajczak B;Xu J;Yates A;Zerbino D;Zhang Y;Aken B;Choudhary JS;Gerstein M;Guigó R;Hubbard TJP;Kellis M;Paten B;Reymond A;Tress ML;Flicek P
通讯作者：
Flicek P
影响因子：
4.5
作者：
Pai AA;Pritchard JK;Gilad Y
通讯作者：
Gilad Y
影响因子：
7
作者：
Harrow J;Frankish A;Gonzalez JM;Tapanari E;Diekhans M;Kokocinski F;Aken BL;Barrell D;Zadissa A;Searle S;Barnes I;Bignell A;Boychenko V;Hunt T;Kay M;Mukherjee G;Rajan J;Despacio-Reyes G;Saunders G;Steward C;Harte R;Lin M;Howald C;Tanzer A;Derrien T;Chrast J;Walters N;Balasubramanian S;Pei B;Tress M;Rodriguez JM;Ezkurdia I;van Baren J;Brent M;Haussler D;Kellis M;Valencia A;Reymond A;Gerstein M;Guigó R;Hubbard TJ
通讯作者：
Hubbard TJ
DOI：
10.1126/science.1262110
发表时间：
2015-05-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
GTEx Consortium
通讯作者：
GTEx Consortium