Relating mutant genotype to phenotype via quantitative behavior of the NADPH redox cycle in human erythrocytes.

ABSTRACT:

Background

The NADPH redox cycle plays a key role in antioxidant protection of human erythrocytes. It consists of two enzymes: glucose-6-phosphate dehydrogenase (G6PD) and glutathione reductase. Over 160 G6PD variants have been characterized and associated with several distinct clinical manifestations. However, the mechanistic link between the genotype and the phenotype remains poorly understood.

Methodology/principal findings

We address this issue through a novel framework (design space) that integrates information at the genetic, biochemical and clinical levels. Our analysis predicts three qualitatively-distinct phenotypic regions that can be ranked according to fitness. When G6PD variants are analyzed in design space, a correlation is revealed between the phenotypic regio

SUBMITTER: Coelho PM 

PROVIDER: S-EPMC2946920 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature