Browsing by Subject "Chromosomes, Mammalian"

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    ItemOpen Access
    Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs.
    (Nature, 2002-12-05) Okazaki, Y; Furuno, M; Kasukawa, T; Adachi, J; Bono, H; Kondo, S; Nikaido, I; Osato, N; Osato, N; Saito, R; Suzuki, H; Yamanaka, I; Kiyosawa, H; Yagi, K; Tomaru, Y; Hasegawa, Y; Nogami, A; Schönbach, C; Gojobori, T; Baldarelli, R; Hill, DP; Bult, C; Hume, DA; Hume, DA; Quackenbush, J; Schriml, LM; Kanapin, A; Matsuda, H; Batalov, S; Beisel, KW; Blake, JA; Bradt, D; Brusic, V; Chothia, C; Corbani, LE; Cousins, S; Dalla, E; Dragani, TA; Fletcher, CF; Forrest, A; Frazer, KS; Gaasterland, T; Gariboldi, M; Gissi, C; Godzik, A; Gough, J; Grimmond, S; Gustincich, S; Hirokawa, N; Jackson, IJ; Jarvis, ED; Kanai, A; Kawaji, H; Kawasawa, Y; Kedzierski, RM; King, BL; Konagaya, A; Kurochkin, IV; Lee, Y; Lenhard, B; Lyons, PA; Maglott, DR; Maltais, L; Marchionni, L; McKenzie, L; Miki, H; Nagashima, T; Numata, K; Okido, T; Pavan, WJ; Pertea, G; Pesole, G; Petrovsky, N; Pillai, R; Pontius, JU; Qi, D; Ramachandran, S; Ravasi, T; Reed, JC; Reed, DJ; Reid, J; Ring, BZ; Ringwald, M; Sandelin, A; Schneider, C; Semple, CAM; Setou, M; Shimada, K; Sultana, R; Takenaka, Y; Taylor, MS; Teasdale, RD; Tomita, M; Verardo, R; Wagner, L; Wahlestedt, C; Wang, Y; Watanabe, Y; Wells, C; Wilming, LG; Wynshaw-Boris, A; Yanagisawa, M; Yang, I; Yang, L; Yuan, Z; Zavolan, M; Zhu, Y; Zimmer, A; Carninci, P; Hayatsu, N; Hirozane-Kishikawa, T; Konno, H; Nakamura, M; Sakazume, N; Sato, K; Shiraki, T; Waki, K; Kawai, J; Aizawa, K; Arakawa, T; Fukuda, S; Hara, A; Hashizume, W; Imotani, K; Ishii, Y; Itoh, M; Kagawa, I; Miyazaki, A; Sakai, K; Sasaki, D; Shibata, K; Shinagawa, A; Yasunishi, A; Yoshino, M; Waterston, R; Lander, ES; Rogers, J; Birney, E; Hayashizaki, Y; FANTOM Consortium; RIKEN Genome Exploration Research Group Phase I & II Team
    Only a small proportion of the mouse genome is transcribed into mature messenger RNA transcripts. There is an international collaborative effort to identify all full-length mRNA transcripts from the mouse, and to ensure that each is represented in a physical collection of clones. Here we report the manual annotation of 60,770 full-length mouse complementary DNA sequences. These are clustered into 33,409 'transcriptional units', contributing 90.1% of a newly established mouse transcriptome database. Of these transcriptional units, 4,258 are new protein-coding and 11,665 are new non-coding messages, indicating that non-coding RNA is a major component of the transcriptome. 41% of all transcriptional units showed evidence of alternative splicing. In protein-coding transcripts, 79% of splice variations altered the protein product. Whole-transcriptome analyses resulted in the identification of 2,431 sense-antisense pairs. The present work, completely supported by physical clones, provides the most comprehensive survey of a mammalian transcriptome so far, and is a valuable resource for functional genomics.
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    ItemOpen Access
    Candidate genes on murine chromosome 8 are associated with susceptibility to Staphylococcus aureus infection in mice and are involved with Staphylococcus aureus septicemia in humans.
    (PloS one, 2017-01) Yan, Qin; Ahn, Sun Hee; Medie, Felix Mba; Sharma-Kuinkel, Batu K; Park, Lawrence P; Scott, William K; Deshmukh, Hitesh; Tsalik, Ephraim L; Cyr, Derek D; Woods, Christopher W; Yu, Chen-Hsin Albert; Adams, Carlton; Qi, Robert; Hansen, Brenda; Fowler, Vance G
    We previously showed that chromosome 8 of A/J mice was associated with susceptibility to S. aureus infection. However, the specific genes responsible for this susceptibility are unknown. Chromosome substitution strain 8 (CSS8) mice, which have chromosome 8 from A/J but an otherwise C57BL/6J genome, were used to identify the genetic determinants of susceptibility to S. aureus on chromosome 8. Quantitative trait loci (QTL) mapping of S. aureus-infected N2 backcross mice (F1 [C8A] × C57BL/6J) identified a locus 83180780-88103009 (GRCm38/mm10) on A/J chromosome 8 that was linked to S. aureus susceptibility. All genes on the QTL (n~ 102) were further analyzed by three different strategies: 1) different expression in susceptible (A/J) and resistant (C57BL/6J) mice only in response to S. aureus, 2) consistently different expression in both uninfected and infected states between the two strains, and 3) damaging non-synonymous SNPs in either strain. Eleven candidate genes from the QTL region were significantly differently expressed in patients with S. aureus infection vs healthy human subjects. Four of these 11 genes also exhibited significantly different expression in S. aureus-challenged human neutrophils: Ier2, Crif1, Cd97 and Lyl1. CD97 ligand binding was evaluated within peritoneal neutrophils from A/J and C57BL/6J. CD97 from A/J had stronger CD55 but weaker integrin α5β1 ligand binding as compared with C57BL/6J. Because CD55/CD97 binding regulates immune cell activation and cytokine production, and integrin α5β1 is a membrane receptor for fibronectin, which is also bound by S. aureus, strain-specific differences could contribute to susceptibility to S. aureus. Down-regulation of Crif1 with siRNA was associated with increased host cell apoptosis among both naïve and S. aureus-infected bone marrow-derived macrophages. Specific genes in A/J chromosome 8, including Cd97 and Crif1, may play important roles in host defense against S. aureus.
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    Two genes on A/J chromosome 18 are associated with susceptibility to Staphylococcus aureus infection by combined microarray and QTL analyses.
    (PLoS Pathog, 2010-09-02) Ahn, SH; Deshmukh, H; Johnson, N; Cowell, LG; Rude, TH; Scott, WK; Nelson, CL; Zaas, AK; Marchuk, DA; Keum, S; Lamlertthon, S; Sharma Kuinkel, BK; Sempowski, GD; Fowler Jr, VG
    Although it has recently been shown that A/J mice are highly susceptible to Staphylococcus aureus sepsis as compared to C57BL/6J, the specific genes responsible for this differential phenotype are unknown. Using chromosome substitution strains (CSS), we found that loci on chromosomes 8, 11, and 18 influence susceptibility to S. aureus sepsis in A/J mice. We then used two candidate gene selection strategies to identify genes on these three chromosomes associated with S. aureus susceptibility, and targeted genes identified by both gene selection strategies. First, we used whole genome transcription profiling to identify 191 (56 on chr. 8, 100 on chr. 11, and 35 on chr. 18) genes on our three chromosomes of interest that are differentially expressed between S. aureus-infected A/J and C57BL/6J. Second, we identified two significant quantitative trait loci (QTL) for survival post-infection on chr. 18 using N(2) backcross mice (F(1) [C18A]xC57BL/6J). Ten genes on chr. 18 (March3, Cep120, Chmp1b, Dcp2, Dtwd2, Isoc1, Lman1, Spire1, Tnfaip8, and Seh1l) mapped to the two significant QTL regions and were also identified by the expression array selection strategy. Using real-time PCR, 6 of these 10 genes (Chmp1b, Dtwd2, Isoc1, Lman1, Tnfaip8, and Seh1l) showed significantly different expression levels between S. aureus-infected A/J and C57BL/6J. For two (Tnfaip8 and Seh1l) of these 6 genes, siRNA-mediated knockdown of gene expression in S. aureus-challenged RAW264.7 macrophages induced significant changes in the cytokine response (IL-1 beta and GM-CSF) compared to negative controls. These cytokine response changes were consistent with those seen in S. aureus-challenged peritoneal macrophages from CSS 18 mice (which contain A/J chromosome 18 but are otherwise C57BL/6J), but not C57BL/6J mice. These findings suggest that two genes, Tnfaip8 and Seh1l, may contribute to susceptibility to S. aureus in A/J mice, and represent promising candidates for human genetic susceptibility studies.