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

E41 Identification of Candidate Genes for Blood Pressure (BP) Quantitative Trait Loci (QTL) Based on their Expression Patterns in a Panel of Congenic Rats

Soon Jin Lee, Howard Dene, Jun Liu, Michel R. Garrett, John P. Rapp, and George T. Cicila. Medical College of Ohio, Toledo, OH

We sought candidate genes for BP QTLs present in the Dahl salt-sensitive hypertension model first by identifying genes differentially-expressed in the kidneys of one month old Dahl salt-sensitive (S) and salt-resistant (R) rats using the differential display technique. Kidney RNA expression patterns of these genes were then examined using Northern filter hybridization in a panel of eight different one month old congenic rat strains, where each strain harbors an allele for a different BP QTL on an otherwise uniform background of alleles from the hypertensive S strain. These congenic strains have portions of chromosomes 1, 2, 3, 5, 7, 9, 10 and 13, respectively, from normotensive rat strains introgressed into the S strain. We reason that gene(s) responsible for a particular QTL's effect should show a congenic strain-specific differential pattern of expression in a candidate organ(s) and should map to the chromosomal interval carried by that particular congenic strain. We screened about 15% of the expressed genes in the kidney and identified 18 differentially-expressed genes having three different expression patterns. Four genes showed differential kidney mRNA expression in only R and a single congenic strain, compared to S rats. Twelve genes were differentially expressed in R rats and a subset of the congenic strain panel compared to S rats. We also identified two genes with differential kidney mRNA expression in all congenic rat strains and the R rat, compared to S rats. Eleven differentially-expressed genes have been mapped using a radiation hybrid panel, with one gene mapping to the predicted chromosomal region and three genes mapping near known BP QTL regions on chromosomes other than those predicted by the expression pattern. We also identified three genes with expression patterns suggesting differential expression resulting from epistatic interactions in a "double" congenic strain which had two BP QTL (from chromosomes 2 and 10) introgressed.


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