DEX–specific cis-regulation of MYO6 expression.

(A) The rs646967 SNP located upstream of the MYO6 gene was shown to be strongly associated with MYO6 expression in DEX-treated cells (top left) with no effect in BMP-2 (top middle), PGE-2 (top right) or untreated samples (data not shown). Expression scores from Illumina Ref8 BeadArrays for each individual are averaged from two biological replicates and shown as red circles and the regression line from linear regression model is indicated with blue dashes. (B) The treatment-specific effect of cis-regulation of MYO6 expression was validated by sequencing-based allelic expression test in four samples heterozygous for both the rs646967 cis-eSNP and for the intragenic rs12606 marker. Normalized rs12606 heterozygote allele ratios of RNA samples from DEX (24h), BMP-2 (2h) and PGE2 (24h) treated cells were compared within and between samples and data are presented as mean ± SD of three technical replicates. Significant P-value is obtained from t-test comparing |Δ het ratio| in DEX versus BMP-2 and PGE2 samples. (C) The cis-eQTL analysis of the MYO6 region was expanded by the inclusion of imputed untyped HapMapII SNPs. The P-values from the linear regression analysis represented as −log10(P-value) are shown as vertical bars with a horizontal line indicating a cutoff of P = 10−4. The rs584677 SNP, marked with an arrow, located ∼160kb upstream of the transcription start site showed the most significant association with MYO6 expression.

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