Genome-Wide Analysis of Human SNPs at Long Intergenic Noncoding RNAs
Genome-Wide Analysis of Human SNPs at Long Intergenic Noncoding RNAs
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人类长基因间非编码 RNA 的 SNP 的全基因组分析
DOI：
10.1002/humu.22239
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发表时间：
2013-02-01
期刊：
影响因子：
3.9
通讯作者：
Cui, Qinghua
中科院分区：
文献类型：
--
作者：
Chen, Geng;Qiu, Chengxiang;Cui, Qinghua
长链基因间非编码RNA（lincRNAs）在哺乳动物和其他真核生物的非编码基因中占很大比例，但至今仍是人们了解最少的遗传因子之一。在此，我们在基因组水平上系统地分析了lincRNAs的人类单核苷酸多态性（SNPs）。我们发现lincRNA区域的SNP密度显著低于其上游和下游侧翼区域。lincRNAs中的功能区域比其他区域显示出更低的SNP密度。我们揭示出表达水平较高且表达谱更广的lincRNAs具有显著更低的SNP密度。此外，我们鉴定出了近期受到正选择的lincRNAs，并发现这些lincRNAs在SNP密度、表达水平和组织特异性方面表现出差异。重要的是，我们在一种脑特异性lincRNA中鉴定出一个近期受到正选择的遗传变异（rs7990916：T>C），它显著影响正常大脑的结构。对脑部磁共振图像的分析表明，具有CC基因型的个体比具有TT基因型的个体具有明显更大的局部灰质体积。此外，该SNP的基因型在正常老年人、轻度认知障碍和阿尔茨海默病患者中呈现不同的分布，这表明这种lincRNA可能在人类大脑的生理和病理生理过程中发挥作用。
Long intergenic noncoding RNAs (lincRNAs) represent a large portion of the noncoding genes in mammals and other eukaryotes but remains among the least well-understood of genetic factors to date. Here, we systematically analyzed the human SNPs of lincRNAs at a genome level. We found a significantly lower SNP density in lincRNA regions than both their upstream and downstream flanking regions. Functional regions show lower SNP density than other regions in lincRNAs. We revealed that lincRNAs with higher expression levels and broader expression spectrum have significantly lower SNP density. Moreover, we identified lincRNAs that are under recent positive selection and revealed that these lincRNAs show distinct SNP density, expression level, and tissue specificity. Importantly, we identified a genetic variant (rs7990916:T>C) under recent positive selection at a brain-specific lincRNA that significantly affects the structure of normal brain. Analysis of brain magnetic resonance images showed that individuals with CC genotype have significant bigger regional gray matter volume than individuals with TT genotype. Moreover, the genotype of this SNP shows different distribution in normal elders, mild cognitive impairment, and Alzheimer disease subjects, suggesting that this lincRNA may have a role in physiology and pathophysiology of human brain.