DNA haplotype analyses of patients with hyperphenylalaninemia.

Linkage analysis of phenylketonurics has shown a strong association between the DNA haplotype at the phenylalanine hydroxylase (PAH) locus and phenylketonuria (PKU). Similarly, a genetic linkage between less severe forms of hyperphenylalaninemia (HPA) and the PAH locus has been suggested. In the present study we analyzed this linkage in more detail. Haplotypes at the PAH locus were determined for 19 individuals with moderately elevated plasma phenylalanine and normal urinary neopterin/biopterin ratios. Fourteen of these individuals had plasma phenylalanine levels of 4-10 mg/dl (mild HPA), and the other five had plasma phenylalanine levels of 10-19 mg/dl (atypical PKU). Thirteen of the 15 HPA families consisted of an affected child and at least one other sibling. Elevated plasma phenylalanine was seen to genetically segregate with specific PAH alleles in each family. Summation of the LOD scores for both categories of moderate plasma phenylalanine elevation gave a maximum value of 3.556 at theta = 0. At theta = 0 this gives a probability of linkage between the PAH locus and the locus for moderate phenylalanine elevations that is approximately 3,600:1. None of the alleles segregating with either mild HPA or atypical PKU were of haplotype 2 or 3, and 13/20 were of types 1 or 4. This is in agreement with the most deleterious mutations being on haplotypes 2 and 3 and with the less severe mutations being on haplotypes 1 and 4. chi 2 Analyses indicated no statistically significant correlation between HPA and a particular haplotype or restriction-enzyme site.     

Using anticipatory life cycle assessment to enable future sustainable construction

The built environment is the largest single emitter of CO₂ and an important consumer of energy. Much research has gone into the improved efficiency of building operation and construction products. Life Cycle Assessment (LCA) is commonly used to assess existing buildings or building products. Classic LCA, however, is not suited for evaluating the environmental performance of developing technologies. A new approach, anticipatory LCA (a‐LCA), promises various advantages and can be used as a design constraint during the product development stage. It helps overcome four challenges: (i) data availability, (ii) stakeholder inclusion, (iii) risk assessment, and (iv) multi‐criteria problems. This article's contribution to the line of research is twofold: first, it adapts the a‐LCA approach for construction‐specific purposes in theoretical terms for the four challenges. Second, it applies the method to an innovative prefabricated modular envelope system, the CleanTechBlock (CTB), focusing on challenge (i). Thirty‐six CTB designs are tested and compared to conventional walls. Inclusion of technology foresight is achieved through structured scenario analysis. Moreover, challenge (iv) is tackled through the analysis of different environmental impact categories, transport‐related impacts, and thickness of the wall assemblies of the CTB. The case study results show that optimized material choice and product design is needed to reach the lowest environmental impact. Methodological findings highlight the importance of context‐specific solutions and the need for benchmarking new products.