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Putting the genes for type II diabetes on the map

The sequencing of the human genome represents a major milestone that will have profound consequences for the practice of medicine. Many new disease genes will be identified, and this information may someday be used to predict a patient's risk of developing a specific disease or response to a particular drug. The following six News and Views articles discuss how The Human Genome Project will revolutionize the diagnosis and treatment of diseases including diabetes, asthma, cancer, autoimmunity and cardiac disease, as well as the potential for developing 'personalized therapies'. They also serve to remind us that although we have our 'genetic blueprint' in hand, a large amount of work remains before we fully understand how to best use it.

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Figure 1: Location of potential type II diabetes genes.

References

  1. Kahn, C.R. Insulin action, diabetogenes, and the cause of type 2 diabetes. Diabetes 43, 1066–1084 (1994).

    Article  CAS  Google Scholar 

  2. International Human Genome Consortium. Initial sequencing and analysis of the human genome. Nature 409, 860–921 (2001).

  3. Vionnet, N. et al. Nonsense mutation in the glucokinase gene causes early-onset non-insulin-dependent diabetes mellitus Nature 356, 721–722 (1992).

    Article  CAS  Google Scholar 

  4. Yamagata, K. et al. Mutations in the hepatocyte nuclear factor-1α gene in maturity-onset diabetes of the young. Nature 384, 455–458 (1996).

    Article  CAS  Google Scholar 

  5. Stoffers, D.A., Ferrer, J. & Habener, J.F. Early-onset-type-II diabetes mellitus (MODY4) linked to 1PF1. Nature Genet. 2, 138–139 (1997).

    Article  Google Scholar 

  6. Malecki, M.T. et al. Mutations in NEUROD1 are associated with the development of type 2 diabetes mellitus. Nature Genet. 23, 323–328 (1999).

    Article  CAS  Google Scholar 

  7. Krook, A. & O'Rahilly S. Mutant insulin receptors in syndromes of insulin resistance. Baillieres. Clin. Endo. Metab. 10, 97–122 (1996).

    Article  CAS  Google Scholar 

  8. Schon, E.A. Mitochondrial genetics and disease. Trends Biochem. Sci. 55, 555–560 (2000).

    Article  Google Scholar 

  9. Shackleton, S. et al. LMNA, encoding lamin A/C, is mutated in partial lipodystrophy. Nature Genet. 2, 153–156 (2000).

    Article  Google Scholar 

  10. Strom, T.M. et al. Diabetes insipidus, diabetes mellitus, optic atrophy and deafness (DIDMOAD) caused by mutations in a novel gene (wolframin) coding for a predicted transmembrane protein. Hum. Mol. Genet. 7, 2021–2028 (1998).

    Article  CAS  Google Scholar 

  11. Hudson, T.J. et al. An STS-based map of the human genome. Science 270, 1945–1954 (1995).

    Article  CAS  Google Scholar 

  12. Horikawa, Y. et al. Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus. Nature Genet. 26,163–175 (2000).

    Article  CAS  Google Scholar 

  13. Cox, N.J. et al. Loci on chromosomes 2 (NIDDM1) and 15 interact to increase susceptibility to diabetes in Mexican Americans. Nature Genet. 21, 213–215 (1999).

    Article  CAS  Google Scholar 

  14. Ji, L. et al. New susceptibility locus for NIDDM is localized to human chromosome 20q. Diabetes 46, 876–881 (1997).

    Article  CAS  Google Scholar 

  15. Bowden, D.W. et al. Linkage of genetic markers on human chromosomes 20 and 12 to NIDDM in Caucasian sib pairs with a history of diabetic nephropathy. Diabetes 46, 882–886 (1997).

    Article  CAS  Google Scholar 

  16. Zouali, H. et al. A susceptibility locus for early-onset-insulin dependent (type 2) diabetes mellitus maps to chromosome 20q, proximal to the phosphoenolpyruvate carboxykinase gene. Hum. Mol. Genet. 6, 1401–1408 (1997).

    Article  CAS  Google Scholar 

  17. Hanson, R.L. et al. An autosomal genomic scan for loci linked to type II diabetes mellitus and body-mass index in Pima Indians. Am. J. Hum. Genet. 63, 1130–1138 (1998).

    Article  CAS  Google Scholar 

  18. Elbein, S.C., Hoffman, M.D., Teng, K., Leppert, M.F. & Hasstedt, S.J. A genome-wide search for type 2 diabetes susceptibility genes in Utah Caucasians. Diabetes 48, 1175–1182 (1999).

    Article  CAS  Google Scholar 

  19. Ghosh, S. et al. The Finland-United States investigation of non-insulin-dependent diabetes mellitus genetics (FUSION) study. I. An autosomal genome scan for genes that predispose to type 2 diabetes. Am. J. Hum. Genet. 5, 1174–1185 (2000).

    Google Scholar 

  20. Watanabe, R.M. et al. The Finland-United States investigation of non-insulin-dependent diabetes mellitus genetics (FUSION) study. II. An autosomal genome scan for diabetes-related quantitative-trait loci. Am. J. Hum. Genet. 5, 1186–1200 (2000).

    Google Scholar 

  21. Almind, K., Inoue, G., Pedersen, O. & Kahn, C.R. A common amino acid polymorphism in insulin receptor substrate-1 causes impaired insulin signaling. Evidence from transfection studies. J. Clin. Invest. 97, 2569–2575 (1996).

    Article  CAS  Google Scholar 

  22. Yen, C.J. et al. Molecular scanning of the human peroxisome proliferator activated receptor gamma (hPPAR γ) gene in diabetic Caucasians: identification of a Pro12Ala PPAR γ 2 missense mutation. Biochem. Biophys. Res. Commun. 241, 270–274 (1997).

    Article  CAS  Google Scholar 

  23. Altshuler, D. et al. The common PPARγ Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes. Nature Genet. 26, 76–80 (2000).

    Article  CAS  Google Scholar 

  24. Hani, E.H. et al. Defective mutations in the insulin promoter factor-1 (IPF-1) gene in late-onset type 2 diabetes mellitus. J. Clin. Invest. 104, R41–48 (1999).

    Article  CAS  Google Scholar 

  25. The international SNP map working group. A map of human genome sequence variation containing 1.4 million single nucleotide polymorphisms. Nature 409, 928–933 (2001).

  26. Weiss, K.M. & Terwilliger, J.D. How many diseases does it take to map a gene with SNPs? Nature Genet. 26, 151–157, 2000

    Article  CAS  Google Scholar 

  27. Kruglyak, L. Prospects for whole-genome linkage disequilibrium mapping of common disease genes. Nature Genet. 22, 139–144 (1999).

    Article  CAS  Google Scholar 

  28. Bock, J.B., Matern, H.T., Peden, A.A. & Scheller, R.H. A genomic perspective on membrane compartment organization. Nature 409, 839–841 (2001).

    Article  CAS  Google Scholar 

  29. Mokdad, A.H. et al. Diabetes trends in the U.S.: 1990–1998. Diabetes Care 9,1278–1283 (2000) and Diabetes Care 10, 412 (2001).

    Article  Google Scholar 

  30. Bruning, J.C. et al. Development of a novel polygenic model of NIDDM in mice heterozygous for IR and IRS-1 null alleles. Cell 88, 561–572 (1997)

    Article  CAS  Google Scholar 

Download references

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Almind, K., Doria, A. & Kahn, C. Putting the genes for type II diabetes on the map. Nat Med 7, 277–279 (2001). https://doi.org/10.1038/85405

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