Complex haplotypes, copy number polymorphisms and coding variation in two recently divergent mouse strains

Inbred mouse strains provide the foundation for mouse genetics. By selecting for phenotypic features of interest, inbreeding drives genomic evolution and eliminates individual variation, while fixing certain sets of alleles that are responsible for the trait characteristics of the strain. Mouse strains 129Sv (129S5) and C57BL/6J, two of the most widely used inbred lines, diverged from common ancestors within the last century, yet very little is known about the genomic differences between them. By comparative genomic hybridization and sequence analysis of 129S5 short insert libraries, we identified substantial structural variation, a complex fine-scale haplotype pattern with a continuous distribution of diversity blocks, and extensive nucleotide variation, including nonsynonymous coding SNPs and stop codons. Collectively, these genomic changes denote the level and direction of allele fixation that has occurred during inbreeding and provide a basis for defining what makes these mouse strains unique.     

A screen of the complete protein kinase gene family identifies diverse patterns of somatic mutations in human breast cancer

We examined the coding sequence of 518 protein kinases, approximately 1.3 Mb of DNA per sample, in 25 breast cancers. In many tumors, we detected no somatic mutations. But a few had numerous somatic mutations with distinctive patterns indicative of either a mutator phenotype or a past exposure.     

TRPV3 is a temperature-sensitive vanilloid receptor-like protein

Vanilloid receptor-1 (VR1, also known as TRPV1) is a thermosensitive, nonselective cation channel that is expressed by capsaicin-sensitive sensory afferents and is activated by noxious heat, acidic pH and the alkaloid irritant capsaicin. Although VR1 gene disruption results in a loss of capsaicin responses, it has minimal effects on thermal nociception. This and other experiments--such as those showing the existence of capsaicin-insensitive heat sensors in sensory neurons--suggest the existence of thermosensitive receptors distinct from VR1. Here we identify a member of the vanilloid receptor/TRP gene family, vanilloid receptor-like protein 3 (VRL3, also known as TRPV3), which is heat-sensitive but capsaicin-insensitive. VRL3 is coded for by a 2,370-base-pair open reading frame, transcribed from a gene adjacent to VR1, and is structurally homologous to VR1. VRL3 responds to noxious heat with a threshold of about 39 degrees C and is co-expressed in dorsal root ganglion neurons with VR1. Furthermore, when heterologously expressed, VRL3 is able to associate with VR1 and may modulate its responses. Hence, not only is VRL3 a thermosensitive ion channel but it may represent an additional vanilloid receptor subunit involved in the formation of heteromeric vanilloid receptor channels.     

Overview of the Alliance for Cellular Signaling

The Alliance for Cellular Signaling is a large-scale collaboration designed to answer global questions about signalling networks. Pathways will be studied intensively in two cells--B lymphocytes (the cells of the immune system) and cardiac myocytes--to facilitate quantitative modelling. One goal is to catalyse complementary research in individual laboratories; to facilitate this, all alliance data are freely available for use by the entire research community.     

A fungus pigment of novel type,and the nature of fungus ‘lignin’

Zusammenfassung In den Früchten des höheren PilzesPolyporus hispidus bildet sichin situ ein ligninähnlicher Stoff durch Oxidation-Polymerisation von Phenolen des Phenylpropantyps, hauptsächlich Hispidin (I), dessen Struktur als Enollacton der 3,4-Dihydroxycinnamoylacetessigsäure erkannt wurde.