Fig. 2: COX7A2L lead cis-eQTL affects mRNA stability.
From: COX7A2L genetic variants determine cardiorespiratory fitness in mice and human
a, Schematic representation of rs4181 location and genotypes. b, rs4181 genotype frequency in all populations combined (data from 1000 Genomes Project phase 3)37. c, Normalized expression of COX7A2L in four representative tissues. Data are from the GTEx database, samples are grouped by genotype. The number of samples per tissue per genotype and the cis-eQTL P values are indicated. The statistical analysis used to determine the P value is described in https://gtexportal.org. d, NES of rs4181 ALT allele on COX7A2L expression in different tissues in the GTEx database. Dot color represents the directionality of the effect (blue, negative; red, positive) and dot size is proportional to the P value. The statistical analysis used to determine the P value is described in https://gtexportal.org. All tissues for which rs4181 is a significant cis-eQTL are shown. Tissues are ordered from bottom to top by P value. e, Schematic representation of the pGL3-promoter luciferase vectors used in f. f, Relative luminescence of HEK-293T cells transfected with pGL3-promoter-empty, pGL3-promoter-3′ UTR-REF or pGL3-promoter-3′ UTR-ALT. Cells were co-transfected with pRL-CMV vector and firefly luminescence was normalized to Renilla luminescence to correct for transfection efficiency (empty n = 8, 3′ UTR-REF n = 8, 3′ UTR-ALT n = 8). g, COX7A2L expression in seven differentiated myotubes lines (REF, n = 3; ALT, n = 4) before and 1 h after inhibition of transcription with actinomycin D (10 μg ml−1). h, Schematic representation of COX7A2L mRNA REF and ALT alleles. Exons (E1–E3) and 5′ UTR and 3′ UTR are depicted with the repeat present only in the ALT allele shown in red. Data are represented as violin plots and Tukey’s box and whiskers plots (superimposed) (c). Box plots center represents the median, lower and upper hinges represent the first and third quartile (25th and 75th percentiles). The whiskers extend to the largest and smallest value up to 1.5 × IQR from the hinge. IQR, interquartile range. Data points beyond the whiskers are plotted individually. Data are represented as mean ± s.e.m. (f,g). Statistical analysis was conducted by one-way analysis of variance (ANOVA) (f) and two-way ANOVA and Sidak’s multiple comparisons test (g).
