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ore, genetic analysis of WSB mice to determine the causative aspects is likely to shed important insight into b-cell biology and T2D danger. Acknowledgments The authors would like to thank Ms. Katie Lee for her help. SC will be the Canada Analysis Chair inside the Genetics of Obesity and Diabetes along with a Michael Smith Foundation for Well being Analysis Scholar. Author Contributions Conceived and designed the experiments: SMC. Performed the experiments: MMH XH SK. Analyzed the information: MMH SMC. Contributed reagents/materials/analysis tools: JDJ. Revised the manuscript: JDJ. References 1. Weir GC, Bonner-Weir S Five stages of evolving beta-cell dysfunction for the duration of progression to diabetes. Diabetes 53 Suppl three: S1621. 2. Lyssenko V, Laakso M Genetic screening for the LDN193189 (Hydrochloride) supplier threat of type 2 diabetes: worthless or useful Diabetes Care 36 Suppl 2: S120126. three. Florez JC Newly identified loci highlight beta cell dysfunction as a key cause of sort 2 diabetes: exactly where are the insulin resistance genes Diabetologia 51: 11001110. 4. Morris AP, Voight BF, Teslovich TM, Ferreira T, Segre AV, et al. Largescale association analysis gives insights in to the genetic architecture and pathophysiology of type 2 diabetes. Nat Genet 44: 981990. five. Stahl EA, Wegmann D, Trynka G, Gutierrez-Achury J, Do R, et al. Bayesian inference analyses on the polygenic architecture of rheumatoid arthritis. Nat Genet 44: 483489. 6. Clee SM, Attie AD The genetic landscape of kind two diabetes in mice. Endocr Rev 28: 4883. 7. Bhatnagar S, Oler AT, Rabaglia ME, Stapleton DS, Schueler KL, et al. Positional cloning of a form two diabetes quantitative trait locus; tomosyn-2, a unfavorable regulator of insulin secretion. PLoS Genet 7: e1002323. 8. Clee SM, Yandell BS, Schueler KM, Rabaglia ME, Richards OC, et al. Positional cloning of Sorcs1, a kind 2 diabetes quantitative trait locus. Nat Genet 38: 688693. 9. Goodarzi MO, Lehman DM, Taylor KD, Guo X, Cui J, et al. SORCS1: A Novel Human Kind two Diabetes Susceptibility Gene Suggested by the Mouse. Diabetes 56: 19221929. 10. Dokmanovic-Chouinard M, Chung WK, Chevre JC, Watson E, Yonan J, et al. Positional cloning of ��Lisch-Like, a candidate modifier of susceptibility to sort 2 diabetes in mice. PLoS Genet 4: e1000137. 11. Scherneck S, Nestler M, Vogel H, Bluher M, Block MD, et al. Positional cloning of zinc finger domain transcription aspect Zfp69, a candidate gene for obesity-associated diabetes contributed by mouse locus Nidd/SJL. PLoS Genet 5: e1000541. 12. Keane TM, Goodstadt L, Danecek P, White MA, Wong K, et al. Mouse genomic variation and its effect on phenotypes and gene regulation. Nature 477: 289294. 13. Roberts A, Pardo-Manuel de Villena F, Wang W, McMillan L, Threadgill DW The polymorphism architecture of mouse genetic resources elucidated employing genome-wide resequencing data: implications for QTL discovery and systems genetics. Mamm Genome 18: 473481. 14. Aylor DL, Valdar W, Foulds-Mathes W, Buus RJ, Verdugo RA, et al. Genetic evaluation of complicated traits in the emerging Collaborative Cross. Genome Res 21: 12131222. 15. Sanger Institute Mouse Genomes Project. http://www.sanger.ac.uk/ resources/mouse/genomes/. Accessed 2010 February 24. 16. Collaborative Cross Consortium The genome architecture of the Collaborative Cross mouse genetic reference population. Genetics 190: 389 401.