Genetic basis of transcriptome differences between the founder strains of the rat HXB/BXH recombinant inbred panel
- Equal contributors
1 Genome Biology Group, Hubrecht Institute, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
2 Physiological Genomic and Medicine Group, Medical Research Councils Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London W12 ONN, UK
3 Genomics Laboratory, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London W12 ONN, UK
4 Genome Sciences Centre, BC Cancer Agency, Suite 100 570 West 7th Avenue, Vancouver, British Columbia, Canada V5Z 4S6
5 Institute of Physiology, Academy of Sciences of the Czech Republic, Videnska 1083, 14220 Prague 4, Czech Republic
Genome Biology 2012, 13:r31 doi:10.1186/gb-2012-13-4-r31Published: 27 April 2012
With the advent of next generation sequencing it has become possible to detect genomic variation on a large scale. However, predicting which genomic variants are damaging to gene function remains a challenge, as knowledge of the effects of genomic variation on gene expression is still limited. Recombinant inbred panels are powerful tools to study the cis and trans effects of genetic variation on molecular phenotypes such as gene expression.
We generated a comprehensive inventory of genomic differences between the two founder strains of the rat HXB/BXH recombinant inbred panel: SHR/OlaIpcv and BN-Lx/Cub. We identified 3.2 million single nucleotide variants, 425,924 small insertions and deletions, 907 copy number changes and 1,094 large structural genetic variants. RNA-sequencing analyses on liver tissue of the two strains identified 532 differentially expressed genes and 40 alterations in transcript structure. We identified both coding and non-coding variants that correlate with differential expression and alternative splicing. Furthermore, structural variants, in particular gene duplications, show a strong correlation with transcriptome alterations.
We show that the panel is a good model for assessing the genetic basis of phenotypic heterogeneity and for providing insights into possible underlying molecular mechanisms. Our results reveal a high diversity and complexity underlying quantitative and qualitative transcriptional differences.