Table 1.
Distribution of cases and controls by study center and by ethnicity in the BCFR.
Fig 1.
ABRAXAS multiple-sequence alignment.
Substitution designations are indicated above the corresponding human reference sequence residue. Amino acid symbols are colored to represent standard Dayhoff groupings.
Table 2.
Distribution of ABRAXAS rare variants (i.e. with a minor allele frequency<1% in the Exome Variant Server (EVS)) identified in the BCFR.
Table 3.
Analysis of potentially pathogenic ABRAXAS in-frame deletion or rare missense substitutions.
Table 4.
Distribution of p.Thr141Ile, p.Ser7Ser and p.Ser11Ser by race/ethnicity.
Table 5.
Stratified analyses of the common SNP rs13125836 (c. 1117G>A, p.Asp373Asn) on breast cancer risk in the BCFR.
Fig 2.
p.Gly39val and p.Thr141Ile ABRAXAS mutants have defects in gamma-H2AX formation.
(A) Typical DNA damage foci of ABRAXAS in shABRAXAS (shABX145) MCF7 cells complemented with ABRAXAS-HA-Flag, ABRAXAS-HA-Flag pThr141Ile, or ABRAXAS-HA-Flag pGly39Val. The anti-Flag antibody was used to monitor ABRAXAS foci formation (green), anti-gamma-H2AX (red) and the merge picture is depicted. In blue, DAPI staining. (B) Quantification of gamma-H2AX foci formation in MCF7 cells after neocarzinostatin treatment and release. P-values were obtained with a Wilcoxon’s Test with N = 100 cells from four independent experiments.
Fig 3.
Functional assays assessing the impact of variant rs145796091 c.21G>A (p.Ser7Ser) on transcriptional activity and splicing efficiency in the MCF7 breast cancer cell line.
A) Gene reporter assays. Luciferase activity was normalized to Renilla luciferase. Each experiment was performed three times. Data from four replicates per construct were analyzed with a mixed model including the fixed effect of genotype and the random effects of experiment number and clone within experiment number. B) Splicing reporter mini-gene assays. Mini-gene constructions: exons 1, 2 and 3 of ABRAXAS were subcloned in a pcDNA3.1 vector. C) Gel-electrophoresis of mini-gene RT-PCR products on 2% agarose gels.