International Mammalian Genome Society

The 13th International Mouse Genome Conference
October 31-November 3, 1999

Table of Contents * Structure * Bioinformatics * Sequence * Mapping * New Tools * Gene Discovery * Developmental * Mutagenesis * Functional Genomics

E54 Localization of Rat Chromosome 1 Blood Pressure Quantitative Trait Loci Using Congenic Strains

Yasser Saad, Michael Garrett, Soon Jin Lee, Howard Dene, and John P. Rapp. Department of Physiology and Molecular Medicine, Medical College of Ohio, 3035 Arlington Avenue, Toledo, Ohio 43614-5804

A whole genome scan of an F2(S X LEW) population suggested that two quantitative trait loci (QTL) near the D1Mco1 and Sa markers on rat chromosome 1 were linked to blood pressure with a LOD of 3.0 and 2.4, respectively. To further localize and characterize chromosome 1 QTL, congenic strains were constructed by introgressing the Lewis low-blood-pressure QTL alleles onto the genetic background of the Dahl salt-sensitive (S) rat. Polymerase chain reaction genotyping with microsatellite markers was used to confirm the genotype of the congenic strains. Blood pressure of the congenic strain is compared to that of the S rat using the tail-cuff method after feeding the rats a 2% NaCl diet for 24 days. When compared to the S rat, the congenic strain spanning from the D1Mco2 to the D1Mco35 marker (118cM) lowered blood pressure by 35 mmHg (P<0.0001) indicating that a blood pressure QTL was "trapped" in the congenic region. Congenic substrains with shorter introgressed regions narrowed down the region containing the QTL to the 25cM segment flanked by the D1M7Mit87 and D1N64 markers. There was also a significant effect on heart weight, but no effect on body weight between the congenic substrain and the S rat strain. The Sa gene, which has been reported to be differentially expressed in the kidneys of salt-sensitive and salt-resistant rat strains, was excluded as a blood pressure QTL in the S rat versus Lewis comparison, since it fell within a congenic substrain that showed no effect on blood pressure. A second QTL was localized to a larger segment (45cM) flanked by the D1Uia8 and D1Rat95 markers. Comparison of the blood pressure effects using other congenic substrains will help further localize the size of the region and identify genes on chromosome 1 that are involved in the regulation of blood pressure.


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