Many little things: one geneticist's view of complex diseases.

作者: Oliver Smithies

DOI: 10.1038/NRG1605

关键词:

摘要: Gene targeting is commonly used to knock out genes in order understand their function. It has also been successfully model the relatively rare human genetic diseases that are caused by homozygous loss of gene Modelling much more common multifactorial have strong and environmental causes less easy. Here, I describe my personal voyage into this challenging field, using alter expression impact on hypertension diabetes.

参考文章(32)
Barry M. Brenner, John H. Laragh, Hypertension : pathophysiology, diagnosis, and management Raven Press. ,(1995)
P Niederberger, R Prasad, G Miozzari, H Kacser, A strategy for increasing an in vivo flux by genetic manipulations. The tryptophan system of yeast Biochemical Journal. ,vol. 287, pp. 473- 479 ,(1992) , 10.1042/BJ2870473
O. Smithies, Why the kidney glomerulus does not clog: A gel permeation/diffusion hypothesis of renal function Proceedings of the National Academy of Sciences of the United States of America. ,vol. 100, pp. 4108- 4113 ,(2003) , 10.1073/PNAS.0730776100
Nobuyuki Takahashi, Oliver Smithies, Human genetics, animal models and computer simulations for studying hypertension☆ Trends in Genetics. ,vol. 20, pp. 136- 145 ,(2004) , 10.1016/J.TIG.2004.01.004
A. G. Ogston, The spaces in a uniform random suspension of fibres Transactions of the Faraday Society. ,vol. 54, pp. 1754- 1757 ,(1958) , 10.1039/TF9585401754
W. Huang, Y. Gallois, N. Bouby, P. Bruneval, D. Heudes, M.-F. Belair, J. H. Krege, P. Meneton, M. Marre, O. Smithies, F. Alhenc-Gelas, Genetically increased angiotensin I-converting enzyme level and renal complications in the diabetic mouse. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 98, pp. 13330- 13334 ,(2001) , 10.1073/PNAS.231476798
Kirk R. Thomas, Mario R. Capecchi, Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells Cell. ,vol. 51, pp. 503- 512 ,(1987) , 10.1016/0092-8674(87)90646-5
P. Hilbert, K. Lindpaintner, J. S. Beckmann, T. Serikawa, F. Soubrier, C. Dubay, P. Cartwright, B. De Gouyon, C. Julier, S. Takahasi, M. Vincent, D. Ganten, M. Georges, G. M. Lathrop, Chromosomal mapping of two genetic loci associated with blood-pressure regulation in hereditary hypertensive rats. Nature. ,vol. 353, pp. 521- 529 ,(1991) , 10.1038/353521A0
H. S. Kim, J. H. Krege, K. D. Kluckman, J. R. Hagaman, J. B. Hodgin, C. F. Best, J. C. Jennette, T. M. Coffman, N. Maeda, O. Smithies, Genetic control of blood pressure and the angiotensinogen locus. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 92, pp. 2735- 2739 ,(1995) , 10.1073/PNAS.92.7.2735