Cell cycle expression patterns are highly correlated in F2 islets

1. A sub-group of transcripts that are positively correlated Cell cycle expression patterns are highly correlated in F2 islets

2. A sub-group of transcripts that are positively correlated F2 mice are stratified by cell cycle expression patterns lower insulin higher glucose lower # islets higher TG lower body weight lower c-peptide “non-diabetic” “diabetic”

3. Distribution of a few cell cycle genes in F2 islets Is this difference in the expression of cell cycle genes sufficient to play a role in causing diabetes in the F2 mice?

4. Islet genes with “Regulation of progression through cell cycle” GO term Genome-wide linkage of cell cycle regulatory transcripts

5. Adipose genes with “Regulation of progression through cell cycle” GO term Genome-wide linkage of cell cycle regulatory transcripts

6. Islet genes with “Regulation of progression through cell cycle” GO term eQTL linkage on Chr 2 for cell cycle genes in islet

7. Islet genes with “Regulation of progression through cell cycle” GO term eQTL linkage on Chr 2 for cell cycle genes in islet

8. Islet genes with “Regulation of progression through cell cycle” GO term cis and trans eQTLs on Chr 2 for cell cycle regulation Gene Chr Mb Cdk5rap1 2 153.8 E2f1 2 154.0 Rbl1 (p107) 2 156.6 Igf2 7 137.1 Aip 19 39.0 LOD

9. Ccnh Cdkn2b Ccnd1 Strong cell cycle linkages occur across the genome Pdgfb Foxa2 Cdk3 Rb1 Ccnk LOD

11. body wt. # transcripts (divided by 20) with eQTL lod > 2

12. cell cycle module Co-expression modules identified in female F2 islets F2 female islet network MDS plot

13. Expression heat map for female F2 islets ~7500 transcripts in 14 modules cell cycle 228 female F2 mice

14. Cell cycle genes common in time course and F2 female islet modules

15. Genome-wide mapping of cell cycle gene set in F2 islets Nfx1 nuclear transcription factor, x-box binding 1 Chr 4, 41.1 Mb Prc1 protein regulator of cytokenesis 1 Chr 7, 80.1 Mb LOD Nrm nurim Chr 17, 35.4 Mb

16. LOD rescaled for each transcript, p-value threshold = 0.05 Genome-wide mapping of cell cycle gene set in F2 islets

17. LOD rescaled for each transcript, p-value threshold = 1.0 (will include all traits) Genome-wide mapping of cell cycle gene set in F2 islets

18. LOD rescaled for each transcript, p-value threshold = 1.0 (will include all traits) Mapping of cell cycle gene set in F2 islets to putative “hot spots”

19. LOD not rescaled for each transcript p-value threshold = 1.0 (will include all traits) Mapping other modules in female F2 islets F2 female islet network