Denaturing high-performance liquid chromatography (DHPLC)-based prenatal diagnosis for tuberous sclerosis

Tuberous sclerosis (TSC) is a frequent autosomal-dominant condition (affecting 1 in 6000 individuals) caused by various mutations in either the hamartin (TSC1) or the tuberin gene (TSC2). This allelic and non-allelic heterogeneity makes genetic counseling and prenatal diagnosis difficult, especially as a significant proportion of TSC cases are due to de novo mutations. For this reason the identification of the disease causing mutation is mandatory for accurate counseling, yet current mutation detection methods such as single-strand conformation polymorphism (SSCP) or denaturing gradient gel electrophoresis (DGGE) are labor intensive with limited detection efficiency. Denaturing high-performance liquid chromatography (DHPLC) is a high-throughput, semi-automated mutation detection system with a reported mutation detection rate close to 100% for PCR fragments of up to 800 bp. We used a recently described DHPLC assay allowing the efficient detection of mutations in TSC1 to analyze the DNA extracted from a chorion villus sample in order to perform a prenatal diagnosis for TSC. The fetus was found not to have inherited the deleterious mutation and the DHPLC diagnosis was confirmed by haplotype analysis. This represents the first DHPLC-based prenatal diagnosis of a genetic disease. Copyright © 2001 John Wiley & Sons, Ltd.     

Rational pricing of groundwater with a growing population

When population is increasing, characterizing the optimal water consumption path is complicated by the fact that the underlying dynamics of the water stock is contingent on the level of the stock itself. We propose a method of constructing the optimal path in this case. Since population is increasing, the optimal consumption path may involve refraining at times from consuming the totality of the surface water flow in order to restock in groundwater for future consumption. The aquifer then serves as a means to achieve welfare increasing intertemporal transfers of surface water. Therefore the aquifer itself, as distinct from the stock of water it serves to store, may have value and the marginal valuation of water when groundwater stocks are being drawn upon should, for this reason, differ at times from the marginal valuation of water when it is drawn strictly from surface water.