Determination of dosage compensation of the mammalian X chromosome by RNA-seq is dependent on analytical approach
| Autor: | Craig Obergfell, Michael B. Murphy, Robert J Foley, Sahar Elsisi, Nathaniel K. Jue, Seth D. Kasowitz, Sohaib M Qureshi, Rachel J. O’Neill, Michael J. O'Neill |
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| Jazyk: | angličtina |
| Předmět: |
X Chromosome
Statistics as Topic Paralogous Gene Biology 03 medical and health sciences Mice 0302 clinical medicine Dosage Compensation Genetic Genetics Animals Humans Dosage compensation Gene X chromosome 030304 developmental biology Gene Library 0303 health sciences Autosome Sequence Analysis RNA Gene Expression Profiling Molecular Sequence Annotation Gene expression profiling Female DNA microarray RNA-seq 030217 neurology & neurosurgery Heterogametic sex Research Article Biotechnology |
| Zdroj: | BMC Genomics |
| ISSN: | 1471-2164 |
| DOI: | 10.1186/1471-2164-14-150 |
| Popis: | Background An enduring question surrounding sex chromosome evolution is whether effective hemizygosity in the heterogametic sex leads inevitably to dosage compensation of sex-linked genes, and whether this compensation has been observed in a variety of organisms. Incongruence in the conclusions reached in some recent reports has been attributed to different high-throughput approaches to transcriptome analysis. However, recent reports each utilizing RNA-seq to gauge X-linked gene expression relative to autosomal gene expression also arrived at diametrically opposed conclusions regarding X chromosome dosage compensation in mammals. Results Here we analyze RNA-seq data from X-monosomic female human and mouse tissues, which are uncomplicated by genes that escape X-inactivation, as well as published RNA-seq data to describe relative X expression (RXE). We find that the determination of RXE is highly dependent upon a variety of computational, statistical and biological assumptions underlying RNA-seq analysis. Parameters implemented in short-read mapping programs, choice of reference genome annotation, expression data distribution, tissue source for RNA and RNA-seq library construction method have profound effects on comparing expression levels across chromosomes. Conclusions Our analysis shows that the high number of paralogous gene families on the mammalian X chromosome relative to autosomes contributes to the ambiguity in RXE calculations, RNA-seq analysis that takes into account that single- and multi-copy genes are compensated differently supports the conclusion that, in many somatic tissues, the mammalian X is up-regulated compared to the autosomes. |
| Databáze: | OpenAIRE |
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