Document Type
Article
Disciplines
Life Sciences
Abstract
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.
Recommended Citation
Jue, Nathaniel K.; Murphy, Michael B.; Kasowitz, Seth D.; Qureshi, Sohaib M.; Obergfell, Craig J.; Elsisi, Sahar; Foley, Robert J.; O’Neill, Rachel J.; and O’Neill, Michael J., "Determination of Dosage Compensation of the Mammalian X Chromosome by RNA-seq is Dependent on Analytical Approach" (2013). Open Access Author Fund Awardees' Articles. 11.
https://digitalcommons.lib.uconn.edu/libr_oa/11
Comments
Originally published in :
BMC Genomics 2013, 14:150 doi:10.1186/1471-2164-14-150
The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1471-2164/14/150
© 2013 Jue et al.; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.