Fig. 2
The chromosome 3p teQTL regulates cardiac translation in a protein length-dependent manner. A Circos plot highlighting all distant teQTLs and gene-locus associations detected in the rat heart that associate with the TE of at least 5 genes. The Chr. 3p teQTL is highlighted in dark pink and of the 25 associated genes, only the names of the 11 extracellular matrix (ECM) genes are given. B Overlay of Manhattan plots displaying genome-wide significance values for a genetic association with TE on Chr. 3p. A selection of 5 associated genes whose protein products function in the extracellular matrix are shown. C Scatter plots and square correlation coefficients (r2) based on standardized major axis (SMA) values between coding sequence (CDS) length and the fold change (FC) in gene expression, as measured by Ribo-seq (top) or mRNA-seq (bottom), for heart (left) and liver tissue (right). To define the expression FC, all 30 RI lines are separated by local genotype (BN or SHR) at the Chr. 3p teQTL. For heart Ribo-seq data, the correlation is significant (p value < 2.2 × 10−16; test of correlation coefficient against zero) and the linear model based on fitted SMA method is displayed as a red line. D Schematic overview of the congenic rat lines with isolated teQTL and cardiac mass QTL locus. The SHR.BN-(3L) line carries a local BN genotype, whereas the SHR.BN-(3S) line retains the SHR genotype at the teQTL. Inserted BN segments are visualized in grey, SHR alleles in green. E Scatter plots and square correlation coefficients (r2) based on standardized major axis (SMA) values between coding sequence (CDS) length and the fold change (FC) in gene expression, as measured by Ribo-seq (top) or mRNA-seq (bottom) in congenic rat hearts. The FC in translation is derived from a comparison between 5 replicates of SHR.BN-(3L) and SHR.BN-(3S) rats and reproduces the global length effect observed for the Chr. 3p teQTL identified in the HXB/BXH RI panel. For heart Ribo-seq data, the correlation is significant (p value < 2.2 × 10−16; test of correlation coefficient against zero) and the linear model based on fitted SMA method is displayed as a red line. F Dot plots with indications of mean expression for 2 laminin subunits (extracellular matrix glycoproteins), illustrating the reproducibility of the translational efficiency phenotype between the HXB/BXH RI panel and the congenic rat lines. Cross bars indicate mean values. G Bar plot with all differentially translated genes in a comparison of both congenic rat lines, ordered by Ribo-seq FC in expression. Genes associated with selected significant GO terms are highlighted on top. See also Additional file 1: Figure S3 and Additional file 5: Table S4