The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease

The recycling of the amyloid precursor protein (APP) from the cell surface via the endocytic pathways plays a key role in the generation of amyloid beta peptide (Abeta) in Alzheimer disease. We report here that inherited variants in the SORL1 neuronal sorting receptor are associated with late-onset Alzheimer disease. These variants, which occur in at least two different clusters of intronic sequences within the SORL1 gene (also known as LR11 or SORLA) may regulate tissue-specific expression of SORL1. We also show that SORL1 directs trafficking of APP into recycling pathways and that when SORL1 is underexpressed, APP is sorted into Abeta-generating compartments. These data suggest that inherited or acquired changes in SORL1 expression or function are mechanistically involved in causing Alzheimer disease.     

Genetic mapping with SNP markers in Drosophila.

Map-based positional cloning of Drosophila melanogaster genes is hampered by both the time-consuming, error-prone nature of traditional methods for genetic mapping and the difficulties in aligning the genetic and cytological maps with the genome sequence. The identification of sequence polymorphisms in the Drosophila genome will make it possible to map mutations directly to the genome sequence with high accuracy and resolution. Here we report the identification of 7,223 single-nucleotide polymorphisms (SNPs) and 1,392 insertions/deletions (InDels) in common laboratory strains of Drosophila. These sequence polymorphisms define a map of 787 autosomal marker loci with a resolution of 114 kb. We have established PCR product-length polymorphism (PLP) or restriction fragment-length polymorphism (RFLP) assays for 215 of these markers. We demonstrate the use of this map by delimiting two mutations to intervals of 169 kb and 307 kb, respectively. Using a local high-density SNP map, we also mapped a third mutation to a resolution of approximately 2 kb, sufficient to localize the mutation within a single gene. These methods should accelerate the rate of positional cloning in Drosophila.     

The formation of plagioclase chains during convective transfer in basaltic magma

The basaltic rock in the lower part of the thick Holyoke lava flow in Connecticut and Massachusetts has been shown to have a remarkable texture, with crystals of feldspar linked together in a continuous three-dimensional network of chains. Heating experiments have revealed that this network persists to temperatures where the rock is 75% liquid, and therefore the network was interpreted to have formed at an early stage of crystallization and to have played an important role in the compaction of crystal mush in the lower part of the flow. Despite the texture's importance to our understanding of how such basalt flows form, the origin of the texture has remained uncertain. Here we show that, although the network is present in the lower third of the flow, it was actually formed in the upper solidification front and was transported down in plumes of dense crystal mush. Convection of this type has been postulated for intrusive magma chambers, but corroborative field evidence has been equivocal, especially in lava lakes and flows. Preservation of the roof-generated texture in the lower part of a thick flood-basalt flow therefore constitutes important evidence for the role of convection in the solidification and differentiation of a simple magma sheet.