Integration of the Rat Recombination and EST Maps in the Rat Genomic Sequence and Comparative Mapping Analysis With the Mouse Genome

Abstract

Inbred strains of the laboratory rat are widely used for identifying genetic regions involved in the control of complex quantitative phenotypes of biomedical importance. The draft genomic sequence of the rat now provides essential information for annotating rat quantitative trait locus (QTL) maps. Following the survey of unique rat microsatellite (11,585 including 1648 new markers) and EST (10,067) markers currently available, we have incorporated a selection of 7952 rat EST sequences in an improved version of the integrated linkage-radiation hybrid map of the rat containing 2058 microsatellite markers which provided over 10,000 potential anchor points between rat QTL and the genomic sequence of the rat. A total of 996 genetic positions were resolved (avg. spacing 1.77 cM) in a single large intercross and anchored in the rat genomic sequence (avg. spacing 1.62 Mb). Comparative genome maps between rat and mouse were constructed by successful computational alignment of 6108 mapped rat ESTs in the mouse genome. The integration of rat linkage maps in the draft genomic sequence of the rat and that of other species represents an essential step for translating rat QTL intervals into human chromosomal targets.

Genetic control of plasma lipid levels in a cross derived from normoglycaemic Brown Norway and spontaneously diabetic Goto–Kakizaki rats

“…The markers spanned a total distance of 1,606 cM, which is consistent with our previously published consensus genomewide linkage map of the rat constructed in an F2 cross derived from an identical strain combination [13,14] (ESM Table 2). The calculated average distance between loci was 10.9 cM overall and marker order was consistent with our previously published maps [13,14].…”

“…BN/BN, Homozygous for the BN allele, GK/BN heterozygous, GK/GK homozygous for the GK allele, C cholesterol The permutation LOD scores (10,000 permutations) for these traits that determine statistical significance thresholds varied from 3.50 (LDL cholesterol) to 3.57 (Total cholesterol). mB Megabase *Genetic positions of markers showing the strongest evidence of linkage to lipid variables and 95% CIs were obtained from our high-density reference rat linkage map constructed in a GK×BN cross [13]. **Data derived following the integration of the rat genetic map in the rat genome sequence and comparative genome analyses (http://www.well.ox.ac.uk/rat_mapping_resources) [34].…”

“…Rat genome annotations (http://www.ensembl.org/ Rattus_norvegicus) and comparative genomics [13] provide information on candidate genes at the GK lipid QTLs. The QTL Tchol/gk1 contains numerous candidates, including the sterol carrier protein 2 (Scp2) and clusters of cytochrome P450 and phospholipase A2 genes involved in the synthesis and transport of lipids [36].…”

“…In order to provide optimal genome coverage in the new F2 cross, all markers used in this study were selected in our existing linkage maps derived from a GK×BN F2 cross [13]. Markers were chosen so as to cover the 21 rat chromosomes with an average spacing of 10 to 15 centimorgan (cM) between adjacent loci.…”

Impact of genomics on research in the rat

“…Consequently, most rat research is ultimately translational, aimed at improving human health through the understanding of key genetic and physiological factors in common disease pathways. Using the homologous regions between genomes (Brudno et al 2004;Gibbs et al 2004;Wilder et al 2004) to map diseasecausing genes or regions from one organism to another has begun to bear fruit in humans, a result of the investments into the rat genome project.…”