Figure 2.
Candidate cis-regulated genes within the rat QTL for left ventricular mass. (a) Interval mapping of LVM to chromosome 17p14 in the BXH/HXB RI strain panel. Horizontal dashed line, genome-wide threshold for significance (P = 0.05) of linkage derived by 10,000 permutations; 2-lod support interval region, by vertical box (dotted lines). Positions of the genetic markers are also indicated along the x axis. (b) Volcano plot of significance of cis eQTLs against their relative change in expression. Circles represent 113 transcripts physically encoded within the 2-lod support interval of the QTL and showing cis linkage at their nearest markers (nominal P < 0.05, two-tailed Mann-Whitney U-test). For each transcript, the negative log10 of the P value of linkage is plotted against the relative change in gene expression at the peak of linkage. Dashed horizontal line, significance threshold (P = 0.00033) after Bonferroni correction for multiple testing owing to the number of transcripts in the region that were tested for cis linkage. Transcripts representing Hbld2 (one probe set) and Ogn (two probe sets) are indicated by the arrows. (c) Sequence polymorphisms in Ogn genomic DNA from 2 kb upstream of the first exon to 3 kb downstream of the stop codon. For 5′ UTR, exonic and 3′ UTR variants, positions are reported relative to the start codon; for intronic variants, positions are given relative to the nearest exon. The sequences variation at position 348 in exon 3 of Ogn is synonymous. Ins, insertion. (d) Regulation of Ogn in a blood pressure–independent in vitro model of cardiac myocyte hypertrophy: neonatal rat ventricular myocytes stimulated with phenylephrine for the times shown and assayed by quantitative RT-PCR for changes in Ogn mRNA expression. Mean relative change (± s.e.m.) in gene expression as compared to control samples over the time course of the experiment; *P < 0.05, **P < 0.01.