Fine-mapping and comprehensive transcript analysis reveals nonsynonymous variants within a novel 1.17 Mb Blood Pressure QTL region on Rat Chromosome 10

摘要

The presence of blood pressure (BP) quantitative trait loci (QTL) on rat chromosome (RNO) 10 has been clearly demonstrated by linkage analysis and substitution mapping. Using congenic strains containing the LEW rat chromosomal segments on the Dahl salt-sensitive (S) rat background, further iterations of congenic substrains were constructed and characterized to fine map a chromosome 10 region (QTL1) linked to blood pressure. Comparison of 7 congenic substrains refined QTL1 to a 1.17 Mb segment flanked by D10Mco88 and D10Mco89, which are located at 71,513,116 bp and 72,684,774 bp, respectively. The newly defined QTL1, containing 18 genes, is captured in its entirety within a single congenic substrain. A thorough transcript analysis revealed that three out of these 18 genes, Ccl5, Ddx52 and RGD1559577, had nonsynonymous allelic variations between the S rat and the LEW rat. None of the detected transcripts within the newly defined QTL1 are directly implicated in BP control in humans or model organisms. Therefore, the present work defines a novel blood pressure QTL with three potential quantitative trait nucleotides.