Fig. 1

Luciferase sliding window approach identifies a promoter in the reverse strand of the rs2303751 harboring region. (A) Manhattan plot of the CBE GWAS. The dotted box shows the region harboring ISL15 and is zoomed into (B) Overview of the genomic region where the luciferase is performed referred to the ISL1 gene. In detail, Fragment 1, Fragment 2 and Fragment 3 coordinates are shown relatively to the distance from the ISL1 transcription starting site (TSS) (top) and also in chromosome 5 coordinates (hg38 /lower). Blue and red arrows indicate the orientation of the luciferase-tested fragments. (C) Luciferase assay of the forward (blue) and flipped (red) fragments relative to the empty control vector pGL3 (in gray); significance over control is observed only for the flipped Fragment 2. (D) Fragment 2 luciferase assay with the rs2303751 variant A > G in both forward and flipped orientations displays no significant difference between major (A) and minor (G) allele.