To identify single-nucleotide polymorphisms (SNPs) associated with risk and age at onset of Alzheimer disease (AD) in a genomewide association study of 469 438 SNPs.

To characterize sequences in the RNA helicase‐like PRP2 protein of Saccharomyces cerevisiae that are essential for its function in pre‐mRNA splicing, a pool of random PRP2 mutants was generated. A dominant negative allele was isolated which, when overexpressed in a wild‐type yeast strain, inhibited cell growth by causing a defect in pre‐mRNA splicing. This defect was partially alleviated by simultaneous co‐overexpression of wild‐type PRP2. The dominant negative PRP2 protein inhibited splicing in vitro and caused the accumulation of stalled splicing complexes. Immunoprecipitation with anti‐PRP2 antibodies confirmed that dominant negative PRP2 protein competed with its wild‐type counterpart for interaction with spliceosomes, with which the mutant protein remained associated. The PRP2‐dn1 mutation led to a single amino acid change within the conserved SAT motif that in the prototype helicase eIF‐4A is required for RNA unwinding. Purified dominant negative PRP2 protein had approximately 40% of the wild‐type level of RNA‐stimulated ATPase activity. As ATPase activity was reduced only slightly, but splicing activity was abolished, we propose that the dominant negative phenotype is due primarily to a defect in the putative RNA helicase activity of PRP2 protein.

contributed equally to this workWe have cloned and characterized a new member of the voltage-dependent Ca 2+ channel g subunit family, with a novel gene structure and striking properties. Unlike the genes of other potential g subunits identi®ed by their homology to the stargazin gene, CACNG7 is a ®ve-, and not four-exon gene whose mRNA encodes a protein we have designated g 7 . Expression of human g 7 has been localized speci®cally to brain. N-type current through Ca V 2.2 channels was almost abolished when co-expressed transiently with g 7 in either Xenopus oocytes or COS-7 cells. Furthermore, immunocytochemistry and western blots show that g 7 has this effect by causing a large reduction in expression of Ca V 2.2 rather than by interfering with traf®ck-ing or biophysical properties of the channel. No effect of transiently expressed g 7 was observed on pre-existing endogenous N-type calcium channels in sympathetic neurones. Low homology to the stargazin-like g subunits, different gene structure and the unique functional properties of g 7 imply that it represents a distinct subdivision of the family of proteins identi®ed by their structural and sequence homology to stargazin.

No abstract