RT Journal
A1 Atanur, Santosh S.
A1 Birol, İnanç
A1 Guryev, Victor
A1 Hirst, Martin
A1 Hummel, Oliver
A1 Morrissey, Catherine
A1 Behmoaras, Jacques
A1 Fernandez-Suarez, Xose M.
A1 Johnson, Michelle D.
A1 McLaren, William M.
A1 Patone, Giannino
A1 Petretto, Enrico
A1 Plessy, Charles
A1 Rockland, Kathleen S.
A1 Rockland, Charles
A1 Saar, Kathrin
A1 Zhao, Yongjun
A1 Carninci, Piero
A1 Flicek, Paul
A1 Kurtz, Ted
A1 Cuppen, Edwin
A1 Pravenec, Michal
A1 Hubner, Norbert
A1 Jones, Steven J.M.
A1 Birney, Ewan
A1 Aitman, Timothy J.
T1 The genome sequence of the spontaneously hypertensive rat: Analysis and functional significance
JF Genome Research 
JO Genome Research 
YR 2010 
FD June 01 
VO 20 
IS 6 
SP 791 
OP 803 
DO 10.1101/gr.103499.109 
UL http://genome.cshlp.org/content/20/6/791.abstract 
AB The spontaneously hypertensive rat (SHR) is the most widely studied animal model of hypertension. Scores of SHR quantitative loci (QTLs) have been mapped for hypertension and other phenotypes. We have sequenced the SHR/OlaIpcv genome at 10.7-fold coverage by paired-end sequencing on the Illumina platform. We identified 3.6 million high-quality single nucleotide polymorphisms (SNPs) between the SHR/OlaIpcv and Brown Norway (BN) reference genome, with a high rate of validation (sensitivity 96.3%–98.0% and specificity 99%–100%). We also identified 343,243 short indels between the SHR/OlaIpcv and reference genomes. These SNPs and indels resulted in 161 gain or loss of stop codons and 629 frameshifts compared with the BN reference sequence. We also identified 13,438 larger deletions that result in complete or partial absence of 107 genes in the SHR/OlaIpcv genome compared with the BN reference and 588 copy number variants (CNVs) that overlap with the gene regions of 688 genes. Genomic regions containing genes whose expression had been previously mapped as cis-regulated expression quantitative trait loci (eQTLs) were significantly enriched with SNPs, short indels, and larger deletions, suggesting that some of these variants have functional effects on gene expression. Genes that were affected by major alterations in their coding sequence were highly enriched for genes related to ion transport, transport, and plasma membrane localization, providing insights into the likely molecular and cellular basis of hypertension and other phenotypes specific to the SHR strain. This near complete catalog of genomic differences between two extensively studied rat strains provides the starting point for complete elucidation, at the molecular level, of the physiological and pathophysiological phenotypic differences between individuals from these strains.