Computational protocol: Analysis of functional germline variants in APOBEC3 and driver genes on breast cancer risk in Moroccan study population

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Protocol publication

[…] Regarding driver genes, we focused on genes described to carry BC driver mutations in at least two of the following publications: Stephens et al. 2012; Banerji et al. 2012; Ellis et al. 2012; Shah et al. 2012 [, –]. The well-known and intensively studied genes such as BRCA1 or PTEN were excluded from this study. A total of 36 SNPs across 11 driver genes (ARID1B, ATR, MAP3K1, MLL2, MLL3, NCOR1, RUNX1, SF3B1, SMAD4, TBX3, TTN) and 2 genes of APOBEC3 family (APOBEC3A, APOBEC3B) were selected to the study based on data obtained from Ensembl Genome browser ( for the CEU (Utah residents with Northern and Western European ancestry from the CEPH collection). The SNPs selection was based on these criteria: (1) minor allele frequency (MAF) value over 10 %; (2) location within the coding region (non synonymous SNPs), core promoter regions and 5’- and 3’-untranslated regions (UTRs), (3) Haploview was used to select SNPs on the basis of linkage disequilibrium (LD; r2 ≥ 0.80)) to minimize the number of SNPs to be genotyped. RegulomeDB ( was used to explore the potential function of the associated SNPs. [...] To investigate how the SNPs can influence the gene expression and their consequences on protein binding sites, chromatin structure and promoter and enhancer strength, we used HaploReg ( To identify the possible effects on histone modification we used RegulomeDB ( These effects were proofed for data in MCF7 (Michigan Cancer Foundation-7 breast cancer cell line), T-47D (epithelial cell line derived from mammary ductal carcinoma), HMEC (human mammary epithelial cells) or MCF10A-ER-SRc (breast epithelial cell line -estrogen receptor –src) cell lines. SIFT and PolyPhen predictions were used to determine the possible effect of amino acid substitutions on protein function and structure (Ensemble release 75, The MicroSNiPer was used to predict the impact of all the significant SNPs of this study located in 3’UTR on micro-RNA binding using microSNiPer ( […]

Pipeline specifications

Software tools Haploview, HaploReg, PolyPhen, MicroSNiPer
Databases RegulomeDB
Applications sRNA-seq analysis, GWAS, Genome data visualization
Organisms Homo sapiens
Diseases Breast Neoplasms, Neoplasms
Chemicals Estrogens