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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Assignment of Tangier disease to chromosome 9q31 by a graphical linkage exclusion strategy.

A low level of high density lipoprotein (HDL) cholesterol is a strong predictor of ischaemic heart disease (IHD) and myocardial infarction. One cause of low HDL-cholesterol is Tangier disease (TD), an autosomal codominant inherited condition first described in 1961 in two siblings on Tangier Island in the United States of America. Apart from low HDL-cholesterol levels and an increased incidence of atherosclerosis, TD is characterized by reduced total cholesterol, raised triglycerides, peripheral neuropathy and accumulation of cholesteryl esters in macrophages, which causes enlargement of the liver, spleen and tonsils. In contrast to two other monogenic HDL deficiencies in which defects in the plasma proteins apoA-I and LCAT interfere primarily with the formation of HDL (refs 7-10), TD shows a defect in cell signalling and the mobilization of cellular lipids. The genetic defect in TD is unknown, and identification of the Tangier gene will contribute to the understanding of this intracellular pathway and of HDL metabolism and its link with IHD. We report here the localization of the genetic defect in TD to chromosome 9q31, using a genome-wide graphical linkage exclusion strategy in one pedigree, complemented by classical lod score calculations at this region in a total of three pedigrees (combined lod 10.05 at D9S1784). We also provide evidence that TD may be due to a loss-of-function defect.[1]


  1. Assignment of Tangier disease to chromosome 9q31 by a graphical linkage exclusion strategy. Rust, S., Walter, M., Funke, H., von Eckardstein, A., Cullen, P., Kroes, H.Y., Hordijk, R., Geisel, J., Kastelein, J., Molhuizen, H.O., Schreiner, M., Mischke, A., Hahmann, H.W., Assmann, G. Nat. Genet. (1998) [Pubmed]
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