Effective use of the human and mouse genomes requires reliable identification of genes and their products. Although multiple public resources provide annotation, different methods are used that can result in similar but not identical representation of genes, transcripts, and proteins. The collaborative consensus coding sequence (CCDS) project tracks identical protein annotations on the reference mouse and human genomes with a stable identifier (CCDS ID), and ensures that they are consistently represented on the NCBI, Ensembl, and UCSC Genome Browsers. Importantly, the project coordinates on manually reviewing inconsistent protein annotations between sites, as well as annotations for which new evidence suggests a revision is needed, to progressively converge on a complete protein-coding set for the human and mouse reference genomes, while maintaining a high standard of reliability and biological accuracy. To date, the project has identified 20,159 human and 17,707 mouse consensus coding regions from 17,052 human and 16,893 mouse genes. Three evaluation methods indicate that the entries in the CCDS set are highly likely to represent real proteins, more so than annotations from contributing groups not included in CCDS. The CCDS database thus centralizes the function of identifying well-supported, identically-annotated, protein-coding regions.[Supplemental material is available online at www.genome.org. Data sets and documentation are available in the CCDS database at http://www.ncbi.nlm.nih.gov/CCDS.]One key goal of genome projects is to identify and accurately annotate all protein-coding genes. The resulting annotations add functional context to the sequence data and make it easier to traverse to other rich sources of gene and protein information. Accurately annotating known genes, identifying novel genes, and tracking annotations over time are complex processes that are best achieved through a combination of large-scale computational analyses and expert curation. These methods must (1) process repetitive sequences in multiple categories including retrotransposons, segmental duplications, and paralogs; (2) process variation including copy number variation (CNV) (Feuk et al. 2006) and microsatellites; (3) distinguish functional genes and alleles from pseudogenes; (4) define alternate splice products; and (5) avoid erroneous interpretation based on experimental error.

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Our purposes were to develop a linkage map for rat Chromosome (Chr) 10, using chromosome-sorted DNA, and to construct congenic strains to localize blood pressure quantitative trait loci (QTL) on Chr 10 with the map. The linkage mapping panel consisted of three F2 populations totaling 418 rats. Thirty-two new and 29 known microsatellite markers were placed on the map, which spanned 88.9 centiMorgans (cM). The average distance between markers was 1.46 cM. No markers were separated by more than 6.8 cM. Four congenic strains were constructed by introgressing various segments of Chr 10 from the Milan normotensive strain (MNS) onto the background of the Dahl salt-sensitive (S) strain. A blood pressure QTL with a strong effect on blood pressure (35-42 mm Hg) when expressed on the S background was localized to a 31-cM region between D10Mco6 and D10Mcol. The region does not include the locus for inducible nitric oxide synthase (Nos2), which had been considered to be a candidate locus for the QTL.

SummaryIn vivo experiments were performed to determine whether the cross-linking of membrane immunoglobulin (mlg) D on mature B cells, in the absence of T cell help, leads to B cell death. Mice were injected with either a monoclonal antibody (mAb) that cross-links mlgD effectively or a mAb that binds to mlgD avidly but cross-links it to a limited extent, and effects on B cell number and B cell Ia, mlgM, and mlgD expression were observed. In most experiments, mice were pretreated with anti-interleukin 7 mAb to prevent the generation of new bone marrow B cells, and with anti-CD4 mAb to prevent the generation of T cell help. In some experiments, mice also received anti-Fc3,RII mAb to prevent cross-linking of mlgD with Fc'yRII, and cobra venom factor to prevent possible mlg-complement receptor interactions and complement-mediated T he two-signal theory of B lymphocyte activation predicted that an interaction between antigen and B cell membrane immunoglobulin (mlg) 1 would trigger a B cell-activating event that would lead, in the presence of additional signals, to clonal expansion and antibody production, but, in the absence of additional signals, to death (1). Since this theory was proposed, the cross-linking orB cell mlg has been shown to costimulate B cell proliferation and differentiation in the presence of such stimuli as T cell-produced cytokines (2, 3) and T cell membrane costimulatory molecules (4, 5), while the cross-linking of mlg on newly generated B cells has been shown to lead to B cell unresponsiveness and death (6-8). The ultimate effects of mlg cross-linking on mature B cells, in the absence of additional stimuli, have, however, been less well defined. Cross-linking of mlg, in the absence of T cell help, stimulates enhanced B cell expression of receptors involved in proliferation and cellular interactions (9-11) and, under some conditions, can stimulate DNA synthesis, al-1 Abbreviations used in this paper: GerMS, affinity-purified goat anti-mouse IgD antibody; HEL, hen egg lysozyme; HNA, HBSS supplemented with 10% newborn bovine serum and 0.2% sodium azide; mlg, membrane immunoglobulin. though clonal expansion and antibody secretion are not induced (12-16). It is not known, however, whether these activated B cells eventually return to a resting state, survive but become anergic, or die. This issue has been difficult to resolve in vitro, where unstimulated B cells have a short life span and start to undergo apoptosis within 24 h (17). Study of the effects of mlg cross-linking on B cell life span has also been difficult, in part because of a long-standing controversy about whether resting B cells live for a long or short time in vivo (18)(19)(20)(21)(22). Recent experiments that have either labeled dividing B cells and B cell precursors in vivo (21) or used antibodies to IL-7 to prevent the in vivo generation of new B cells (22) have provided compelling evidence that most mature B cells have a life span that is measurable in weeks, rather than days. This conclusion has made it reasonable to question whe...