Table 1.
Number of differentially expressed genes (up and down-regulated) in different HLNRA dose groups with respect to NLNRA (control group) at different fold changes (1.3, 1.5 and 2.0) with p < 0.05.
Group I refers to background dose level ≤ 1.5mGy/y, Group II: 1.51–5.0 mGy/y, Group III: 5.01–15.0 mGy/y and Group IV: >15.0 mGy/y.
Fig 1.
Histograms showing the number of differentially expressed genes in different HLNRA groups Grp II, Grp III and Grp IV) with respect to NLNRA group (Grp I).
(a) Upregulated genes with adjusted p value < 0.05 (b) Downregulated genes with adjusted p value < 0.05.
Fig 2.
Volcano plots representing the differentially expressed genes (up and down-regulated) at 1.3 fold in different HLNRA groups (Group II, III and IV) as compared to NLNRA (Group I).
A) Group I vs. II, B) Group I vs. III, C) Group I vs. IV. Blue dots represent significant (p<0.05) up-regulated genes and red dots represent significant down- regulated genes.
Fig 3.
Venn diagram showing common as well as unique genes expressed in different group comparisons.
Genes showing ≥ 1.3 fold change was considered for analysis.
Table 2.
Set of differentially expressed genes showing up-regulation at > 1.3 fold change in three HLNRA dose groups (Grp II, Grp III, Grp IV) with respect to NLNRA (Grp I) with adjusted p- value < 0.05.
Table 3.
Set of differentially expressed genes showing down-regulation at > 1.3 fold change in three HLNRA dose groups (Grp II, Grp III, Grp IV) with respect to NLNRA (Grp I) with adjusted p- value < 0.05.
Fig 4.
Representative biological processes (GO analysis) over-represented in differentially expressed genes of high dose groups A) Group III (5.01–15.0 mGy/y) and B) Group IV (>15.0 mGy/y) of HLNRA as compared to Group I (NLNRA).
Table 4.
Representative list of over-represented pathways in higher dose group (Group IV) as compared to NLNRA (Group I).
Fig 5.
Representative heat maps for the respective pathways of up-regulated and down regulated genes in Group IV (high dose group, HLNRA) as compared to NLNRA (Group I).
(a) Representative heat maps for up-regulated genes in Group IV vs Group I (b) Representative heap maps for down regulated genes in Group IV vs Group I. Color panel shows expression intensity levels of genes involved in each pathway.
Fig 6.
Gene ontology analysis showing over-representation of DDR related biological processes to be highly represented in high dose groups (Group III and Group IV) than in Group II.
* shows statistical significance at p < 0.05.
Table 5.
List of important genes involved in various DNA damage response processes.
Fig 7.
Representative heat maps showing intensity values of up and down regulated DNA damage response and repair genes in high dose group (Group IV) of HLNRA as compared to Group I.
Fig 8.
Dose responsive genes showing background dose dependent increase or decrease in expression among different dose groups.
(A) Dose responsive genes showing background dose dependent increase in expression among different dose groups. (B) Dose responsive genes showing background dose dependent decrease in expression among different dose groups. Genes were divided in to three groups A, B and C on the basis of dose response trend shown by them. NLNRA (Group I), HLNRA (Group II, Group III and Group IV).
Fig 9.
Scatter plot showing the expression level of different genes in the individuals belonging to different background dose groups (NLNRA, Group I and HLNRA.
Group II, III and IV) in microarray analysis. Each dot represents normalized value in one individual. Different colored dots represent individuals belonging to different dose groups. Group I (N = 9), Group II (N = 9), Group III (N = 11), Group IV (N = 7).
Fig 10.
Validation of differentially expressed genes using RT q-PCR experiment.
Comparison of fold change values obtained in two different sets of individuals along with microarray results are shown. Blue bar represents microarray results, Red bar shows RT q-PCR results of microarray samples, Green bar shows RT q-PCR results of new set of samples. Fold change values are shown above each bar in all the gene.