國家衛生研究院 NHRI:Item 3990099045/8665
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    题名: Unraveling the association between mRNA expressions and mutant phenotypes in a genome-wide assessment of mice
    作者: Liao, BY;Weng, MP
    贡献者: Division of Biostatistics and Bioinformatics
    摘要: High-throughput gene expression profiling has revealed substantial leaky and extraneous transcription of eukaryotic genes, challenging the perceptions that transcription is strictly regulated and that changes in transcription have phenotypic consequences. To assess the functional implications of mRNA transcription directly, we analyzed mRNA expression data derived from microarrays, RNA-sequencing, and in situ hybridization, together with phenotype data of mouse mutants as a proxy of gene function at the tissue level. The results indicated that despite the presence of widespread ectopic transcription, mRNA expression and mutant phenotypes of mammalian genes or tissues remain associated. The expression-phenotype association at the gene level was particularly strong for tissue-specific genes, and the association could be underestimated due to data insufficiency and incomprehensive phenotyping of mouse mutants; the strength of expression-phenotype association at the tissue level depended on tissue functions. Mutations on genes expressed at higher levels or expressed at earlier embryonic stages more often result in abnormal phenotypes in the tissues where they are expressed. The mRNA expression profiles that have stronger associations with their phenotype profiles tend to be more evolutionarily conserved, indicating that the evolution of transcriptome and the evolution of phenome are coupled. Therefore, mutations resulting in phenotypic aberrations in expressed tissues are more likely to occur in highly transcribed genes, tissue-specific genes, genes expressed during early embryonic stages, or genes with evolutionarily conserved mRNA expression profiles.
    日期: 2015-04-14
    關聯: Proceedings of the National Academy of Sciences of the United States of America. 2015 Apr 14;112(15):4707-4712.
    Link to: http://dx.doi.org/10.1073/pnas.1415046112
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0027-8424&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000352856800058
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84928152192
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