Haplotype differences for copy number variants in the 22q11.23 region among human populations: a pigmentation-based model for selective pressure.

Two gene clusters are tightly linked in a narrow region of chromosome 22q11.23: the macrophage migration inhibitory factor (MIF) gene family and the glutathione S-transferase theta class. Within 120 kb in this region, two 30-kb deletions reach high frequencies in human populations. This gives rise to four haplotypic arrangements, which modulate the number of genes in both families. The variable patterns of linkage disequilibrium (LD) between these copy number variants (CNVs) in diverse human populations remain poorly understood. We analyzed 2469 individuals belonging to 27 human populations with different ethnic origins. Then we correlated the genetic variability of 22q11.23 CNVs with environmental variables. We confirmed an increasing strength of LD from Africa to Asia and to Europe. Further, we highlighted strongly significant correlations between the frequency of one of the haplotypes and pigmentation-related variables: skin color (R2=0.675, P<0.001), distance from the equator (R2=0.454, P<0.001), UVA radiation (R2=0.439, P<0.001), and UVB radiation (R2=0.313, P=0.002). The fact that all MIF-related genes are retained on this haplotype and the evidences gleaned from experimental systems seem to agree with the role of MIF-related genes in melanogenesis. As such, we propose a model that explains the geographic and ethnic distribution of 22q11.23 CNVs among human populations, assuming that MIF-related gene dosage could be associated with adaptation to low UV radiatio

Sustainable Furniture that Grows with End-Users

Economically and environmentally it might be more responsible or even feasible to combine products and services to elongate product lifetime. Gispen, a major office furniture producer in the Netherlands, has embraced circular economic principles to create new business, extend product life time and improve the adaptability of their products. In the Use-it-Wisely (UIW) project two applications were developed. To estimate possible business impacts of adapting a circular economy concept for a company, a dynamic business model simulation has been created by using the system dynamics methodology. And second, Gispen has developed a new Circular Economy Design Framework to support circular product design development. A combination of basic principles to design, upgrade, and reuse products according to circular economy principles are included in the framework as well as a circular life cycle assessment methodology. The development process, non-confidential company results of the tool application and directions for future research are described in this chapter