Title

Determination of Dosage Compensation of the Mammalian X Chromosome by RNA-seq is Dependent on Analytical Approach

Authors

Nathaniel K. Jue, University of Connecticut - Storrs
Michael B. Murphy, University of Connecticut - Storrs
Seth D. Kasowitz, University of Connecticut - Storrs
Sohaib M. Qureshi, University of Connecticut - Storrs
Craig J. Obergfell, University of Connecticut - Storrs
Sahar Elsisi, University of Connecticut - Storrs
Robert J. Foley, University of Connecticut - Storrs
Rachel J. O’Neill, University of Connecticut - Storrs
Michael J. O’Neill, University of Connecticut - Storrs

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.

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.

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