作者
Maya K Leabman, Conrad C Huang, Joseph DeYoung, Elaine J Carlson, Travis R Taylor, Melanie de La Cruz, Susan J Johns, Doug Stryke, Michiko Kawamoto, Thomas J Urban, Deanna L Kroetz, Thomas E Ferrin, Andrew G Clark, Neil Risch, Ira Herskowitz, Kathleen M Giacomini, Pharmacogenetics of Membrane Transporters Investigators¶¶
发表日期
2003/5/13
期刊
Proceedings of the National Academy of Sciences
卷号
100
期号
10
页码范围
5896-5901
出版商
The National Academy of Sciences
简介
Membrane transporters maintain cellular and organismal homeostasis by importing nutrients and exporting toxic compounds. Transporters also play a crucial role in drug response, serving as drug targets and setting drug levels. As part of a pharmacogenetics project, we screened exons and flanking intronic regions for variation in a set of 24 membrane transporter genes (96 kb; 57% coding) in 247 DNA samples from ethnically diverse populations. We identified 680 single nucleotide polymorphisms (SNPs), of which 175 were synonymous and 155 caused amino acid changes, and 29 small insertions and deletions. Amino acid diversity (πNS) in transmembrane domains (TMDs) was significantly lower than in loop domains, suggesting that TMDs have special functional constraints. This difference was especially striking in the ATP-binding cassette superfamily and did not parallel evolutionary conservation: there was …
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MK Leabman, CC Huang, J DeYoung, EJ Carlson… - Proceedings of the National Academy of Sciences, 2003