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人类疾病相关的遗传变异会影响大片段基因间非编码 RNA 的表达。

Human disease-associated genetic variation impacts large intergenic non-coding RNA expression.

机构信息

Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

出版信息

PLoS Genet. 2013;9(1):e1003201. doi: 10.1371/journal.pgen.1003201. Epub 2013 Jan 17.

Abstract

Recently it has become clear that only a small percentage (7%) of disease-associated single nucleotide polymorphisms (SNPs) are located in protein-coding regions, while the remaining 93% are located in gene regulatory regions or in intergenic regions. Thus, the understanding of how genetic variations control the expression of non-coding RNAs (in a tissue-dependent manner) has far-reaching implications. We tested the association of SNPs with expression levels (eQTLs) of large intergenic non-coding RNAs (lincRNAs), using genome-wide gene expression and genotype data from five different tissues. We identified 112 cis-regulated lincRNAs, of which 45% could be replicated in an independent dataset. We observed that 75% of the SNPs affecting lincRNA expression (lincRNA cis-eQTLs) were specific to lincRNA alone and did not affect the expression of neighboring protein-coding genes. We show that this specific genotype-lincRNA expression correlation is tissue-dependent and that many of these lincRNA cis-eQTL SNPs are also associated with complex traits and diseases.

摘要

最近已经清楚,只有一小部分(7%)与疾病相关的单核苷酸多态性(SNP)位于蛋白质编码区,而其余 93%位于基因调控区或基因间区。因此,了解遗传变异如何以组织依赖性方式控制非编码 RNA 的表达具有深远的意义。我们使用来自五个不同组织的全基因组基因表达和基因型数据,测试了 SNP 与大基因间非编码 RNA(lincRNA)表达水平(eQTLs)的关联。我们鉴定了 112 个顺式调控的 lincRNA,其中 45%可以在独立数据集中得到复制。我们观察到,影响 lincRNA 表达的 SNP(lincRNA 顺式 eQTL)中有 75%仅针对 lincRNA 特异性,并且不影响邻近的蛋白质编码基因的表达。我们表明,这种特定的基因型-lincRNA 表达相关性是组织依赖性的,并且许多这些 lincRNA 顺式 eQTL SNP 也与复杂性状和疾病相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9968/3547830/8070dd13c1de/pgen.1003201.g001.jpg

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