Table 2.
Analysis results of the SLC15A4 upstream variant identified in the studied CRC family
| Gene name | Chromosomal position | Variant annotation | Pedigree segregation | NFE allele frequency | CADD v1.6 | Bedtools intersect | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ExAC | gnomAD | CADD SCORE | Chromatin state | TFBS | TFBSPeaksc | Promoter | ||||||||
| ChromHMMa state | ChromHMMa score | Segwayb | Start | End | Strand | |||||||||
| SLC15A4 | 12_129308531_C_T | upstream | III2, III3, III4, III5, IV2 | 0 | 3.75 × 10–3 | 11.38 | TssA | 0.969 | TSS | 52 | 115 | 129,308,487 | 129,308,588 | – |
Chromosomal position, variant annotation, pedigree segregation and allele frequency in the Non-Finnish European (NFE) population are listed. The PHRED-like CADD score, annotation of the chromatin state and location within transcription factor binding sites (TFBS) are derived from CADD v1.6. Affected promoter region according to Bedtools intersect function and SEA, FANTOM5 databases are included with respective start and end positions (Lizio et al. 2015; Wei et al. 2016)
aChromHMM: The ChromHmm score shows the proportion of 127 cell types of the Roadmap Epigenomics project in a particular chromatin state with scores closer to 1 indicating more cell types in the particular chromatin state. The 15 chromatin states are defined as follows: TssA–Active transcription start site (TSS), TssAFInk – Flanking active TSS, TxFlnk–Transcribed at gene 5′ and 3′, Tx–Strong transcription, TxWk–Weak transcription, EnhG–Genic enhancers, Enh–Enhancers, ZNF/Rpts–ZNF genes and repeats, Het–Heterochromatin, TssBiv–Bivalent/Poised TSS/Enhancers, BivFlnk–Flanking bivalent TSS/Enhancer, EnhBiv–Bivalent enhancers, ReprPC–Repressed PolyComb, ReprPCWk–Weak Repressed PolyComb, Quies– Quiescent/low (Ernst and Kellis 2012; Roadmap Epigenomics et al. 2015)
bSegway: Segway uses a genomic segmentation method to annotate the chromatin state based on multiple datasets of ChIP-seq experiments. The chromatin states can be annotated as follows: D–dead, F0/1–FAIRE, R0/1/2/4/5–Repressed Region, H3K9me1–histone 3 lysine 9 monomethylation, L0/1–Low zone, GE0/1/2–Gene body (end),TF0/1/2–Transcription factor activity, C0–CTCF, GS–Gene body (start), E/GM–Enhancer/gene middle, GM0/1–Gene body (middle), TSS–Transcription start site, ZnfRpts–zinc finger repeats (Hoffman et al. 2012)
cTFBS peaks: The number of overlapping ChIP TFBS peaks summed over different cell types/tissue