RNA-seq analyses in pigs: Allelic expression – why make a choice?

O. Madsen, D. Radjabzadeh, H.J. Megens, M. Bosse, L. Frantz, Y. Paudel, R. Crooijmans, L.A. Rund, L.B. Schook, M. Groenen
Proceedings of the 23rd International Conference on Genome Informatics, September 6-9, Hinxton, 2012, United Kingdom


Mono-allelic gene expression is the phenomenon where only one of the parental alleles is expressed and the other is silenced. In recent years it has become increasingly evident that a relative large number of mammalian genes are mono-allelic expressed during mammalian development (Gimelbrant et al. 2007, Keverne 2009). Different forms of mono-allelic expression have been described in mammals, including genomic imprinting, X-chromosome inactivation and allelic exclusion (Zakharova et al. 2009). The three types of mono-allelic expression are all regulated through epigenetic marks such as DNA methylation and histone modification, and by long non-coding RNAs (ncRNAs). Many genes, which do not fall inside one of the three types, have been shown to display mono-allelic expression, with the mono-allelic expression being highly spatial and temporal (Gimelbrant et al. 2007). Mono-allelic expression is wide spread in the mammalian genome and plays important roles in many aspects of mammalian development and diversity, and dysregulation of mono-allelic expressed genes results in a large number of different genetic diseases, including several forms of cancers.
The applicability of high-throughput sequencing methods for detailed discovery of individual genomic variation through whole genome (re-)sequencing and determination of individual variation in allelic expression through NGS transcriptome sequencing (RNA-seq) disclose excellent opportunities for detecting mono-allelic expressed genes (Cooper and Constância 2010). High-throughput sequencing based detection of mono-allelic expressed genes has been applied for human and mouse but is still lacking in most other mammals, including porcine. Pigs is one of the most widely used model organism for human diseases and biomedical research. Thus, a comprehensive investigation of allelic variation in gene expression in pigs will contributes to a more detailed understanding of the evolution of mono-allelic expression in relation to their role in mammalian development, diversity and genetic diseases.
We generated a number of high-throughput whole-genome and RNA-seq data from the same pig individuals plus whole-genome sequences of the parents of two of these individuals, aiming at detection of the different forms of mono-allelic expression. Results of these analyses will be presented and related to mono-allelic expression in other eutherian mammals.