Genetic Variation in Coding Regions Between and Within Commonly Used Inbred Rat Strains

Abstract

Single nucleotide polymorphisms (SNPs) are the most common genetic variation in mammalian populations. Their significance is illustrated by their potential contribution to common disease but also by their potential for use in genetic association and mapping experiments. We have examined the genetic variation between commonly used inbred rat strains by using an efficient SNP discovery and typing assay based on enzyme-based (CEL I) heteroduplex cleavage. Screening of a panel of 96 different rat (sub-)strains for 100 genomic loci in 55 genes, whose human homologs are implicated in clinically relevant diseases like neurological disorder, cancer, schizophrenia, and obesity, resulted in the identification of 103 novel polymorphisms. As all strains are simultaneously genotyped in this setup, this allowed us to make an estimate of the genetic variation between and within commonly used rat inbred strains. Interestingly, we observed substantial genetic variation between colonies of the same inbred strain, maintained at different locations. Furthermore, we identified 17 non-synonymous SNPs that may have an effect on protein function and contribute to phenotypic differences between different laboratory strains.

Circulating hormones and hypothalamic energy balance: regulatory gene expression in the Lou/C and Wistar rats

“…NW047624, obtained from Brown Norway rats, and our sequences. However, these instances of SNPs are not unexpected as considerable genetic variation has previously been observed between Brown Norway compared with Lou/C and Wistar rats (Smits et al 2004). …”

BN phenome: detailed characterization of the cardiovascular, renal, and pulmonary systems of the sequenced rat

“…cgi) (13,29). Furthermore, a growing number of rat strains are or will be resequenced for SNP discovery (1,5,24,29) by two major SNP discovery projects underway in Europe (the Functional Genomics Group in the Netherlands and the MaxDelbruck-Center for Molecular Medicine in Germany) and by Baylor College of Medicine (Houston, TX) via a recent National Human Genome Research Institute white paper to identify SNPs in an additional eight strains. In all, 11 strains, including 7 of the parental strains (or substrains thereof) we present here (F344, FHH, LEW, SD, SS, SHR, and WKY), are being screened or proposed for SNP discovery, with the expected identification of Ͼ485,000 SNPs (1).…”

Novel Integrative Approaches to the Identification of Candidate Genes in Hypertension

“…SHR and BN rats are founder strains for the BXH/HXB RI strains, one of the largest rodent RI panels for analysis of cardiovascular and metabolic phenotypes. 22 The investigation was facilitated by the availability of the reference BN genome sequence, 4 of tens of thousands of rat SNPs, 23,24 of a dense genetic map, 25,26 and of the previous mapping of more than 70 physiological and pathophysiological phenotypes in this RI panel. 27 The next step in the investigation was to use expression levels in the RI strains as "expression" phenotypes, the transcripts being expression traits.…”