A global map for dissecting phenotypic variants in human lincRNAs - PubMed (original) (raw)
A global map for dissecting phenotypic variants in human lincRNAs
Shangwei Ning et al. Eur J Hum Genet. 2013 Oct.
Abstract
Large intergenic noncoding RNAs (lincRNAs) are emerging as key factors of multiple cellular processes. Cumulative evidence has linked lincRNA polymorphisms to diverse diseases. However, the global properties of lincRNA polymorphisms and their implications for human disease remain largely unknown. Here we performed a systematic analysis of naturally occurring variants in human lincRNAs, with a particular focus on lincRNA polymorphism as novel risk factor of disease etiology. We found that lincRNAs exhibited a relatively low level of polymorphisms, and low single-nucleotide polymorphism (SNP) density lincRNAs might have a broad range of functions. We also found that some polymorphisms in evolutionarily conserved regions of lincRNAs had significant effects on predicted RNA secondary structures, indicating their potential contribution to diseases. We mapped currently available phenotype-associated SNPs to lincRNAs and found that lincRNAs were associated with a wide range of human diseases. Some lincRNAs could be responsible for particular diseases. Our results provided not only a global perspective on genetic variants in human lincRNAs but also novel insights into the function and etiology of lincRNA. All the data in this study can be accessed and retrieved freely via a web server at http://bioinfo.hrbmu.edu.cn/lincPoly.
Figures
Figure 1
SNPs in human lincRNAs. (a) The average SNP density in lincRNA, gene and flanking regions. Flanking regions represent adjacent regions with the same length of lincRNAs, and gene regions represent nearest neighboring protein-coding genes of lincRNAs. Error bars are mean±SEM. The _t_-test _P_-values comparing lincRNA regions are shown. (b) The SNP density distribution of ECRs with different lengths. Error bars are mean±SEM.
Figure 2
Structural effects of lincRNA polymorphisms. (a) The predicted MFE change (ΔΔ_G_) distribution for all lincRNA polymorphisms. (b) The predicted MFE change (ΔΔ_G_) distribution for significant lincRNA polymorphisms. (c) The fraction of SNPs in ECRs to all lincRNA polymorphisms, significant lincRNA polymorphisms and lincRNA polymorphisms with larger effects (6≤ΔΔ_G_ ≤7). _P_-values were from _χ_2-tests.
Figure 3
The global map of the phenotype-associated SNPs in human lincRNAs. The gray bands in the outer circle of the map represent the phenotype-associated lincRNAs on each chromosome. The dots in the map represent the phenotype-associated SNPs, with the positions of −log10 (_P_-values), and different colors of dots represent different diseases. Only diseases with at least six SNPs are colored, whereas other diseases are shown in gray. The name of the diseases and the number of SNPs are shown on the bottom right. The bar plots in the inner circles of the map represent the distribution of MFE change (dark orange), SNP density (dark green) and the percent of ECR length (dark blue). We indicated the name of diseases with at least three phenotype-associated SNPs in the lincRNA, as well as those mentioned in the text.
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