Mapping a novel blood pressure quantitative trait locus within a congenic strain spanning a single annotated gene containing segment on rat chromosome 10

Abstract

By high resolution substitution mapping using alleles of the LEW rat introgressed onto the Dahl Salt‐sensitive (S) rat, a 320kb congenic segment was previously identified on rat chromosome 10 (RNO10:70750008‐71070581bp) that further increased the blood pressure (BP) of the S rat. A newer iteration of congenic substrains with introgressed segments ranging from 83kb (70750008‐70832849bp) to 134kb (70750008‐70884058bp) were constructed to further fine‐map this region. Out of these, the systolic BP of the congenic strain spanning a 134kb region was significantly lower compared to that of the S rat by −28 mm Hg (p<0.0001). Bioinformatics analysis of this critical 134kb congenic interval on the rat genome and comparative mapping using mouse and human genomes suggested a single protein coding gene, LOC688668 as the sole candidate gene for this locus. Detailed sequence and expression analyses of this gene will be presented. The significance of this work is that it represents a unique high resolution mapping project wherein the BP lowering effect of the 134kb congenic segment is independently observed when isolated from the longer 320kb congenic segment, which had an overall BP increasing effect.