Figure 1.

Carriers of the rs700635[C] allele show preferential retention of CASP8 intron 8 sequences. RNA-seq data were obtained from normal prostate or breast tissue of donors who were genotyped for rs700635. (A) Median normalized read counts (normalized for each individual to the total number of aligned reads) from prostate RNA were stratified by rs700635 genotype and plotted over the genomic region covering the coding exons of CASP8. Data are from n = 6 C/C homozygotes (shown in red), n = 12 A/C heterozygotes (shown in green) and n = 19 A/A homozygotes (shown in blue). The X-axis is the genomic position in Mb (GRCh37/hg19). The structure of RefSeq CASP8 transcripts in the region is shown beneath the X-axis. (B) Zoom showing prostate RNA median normalized read counts by genotype over the region extending from the 3′ end of intron 7, through the 5′ region of intron 8 up to the NM_033358 variant exon. (C) Similarly plotted median normalized read counts from breast RNA. Data are from n = 7 C/C homozygotes, n = 27 A/C heterozygotes and n = 22 A/A homozygotes. (D) Zoom showing breast RNA median-normalized read counts over a region encompassing the 5′ region of CASP8 intron 8. (E) Association between rs700635 genotype and prostate RNA-seq read count in intron 8. For each individual, the median of normalized RNA-seq read counts overlapping the 5′ region of intron 8 [chr2:202141827-202146555 (GRCh37/hg19)] was determined. Association with genotype was then determined by linear regression against rs700635 variant allele count. P = 3.8 × 10⁻⁸ and β = 0.33 (SD units). (F) Similarly determined association between rs700635 genotype and prostate RNA-seq read count over all major coding exons of CASP8. P = 0.678 and β = −0.07. (G) Association between rs700635 genotype and breast RNA-seq read count in the 5′ region of intron 8. P = 3.11 × 10⁻¹¹ and β = 0.36. (H) Association between rs700635 genotype and breast RNA-seq read count over all CASP8 major coding exons. P = 0.0475 and β = −0.30.