Additional file 6: of Deep genome sequencing and variation analysis of 13 inbred mouse strains defines candidate phenotypic alleles, private variation and homozygous truncating mutations

Private SNPs with multiple VEP consequences. Private SNPs with multiple predicted VEP consequences for each strain strain. Consequence predictions are based on gene models obtained from Ensembl 78. (TXT 66669 kb

Additional file 3: of Deep genome sequencing and variation analysis of 13 inbred mouse strains defines candidate phenotypic alleles, private variation and homozygous truncating mutations

Pairwise variant comparisons. The number of SNPs and indels shared between any two strains contained in the MGP variation catalogue. (XLSX 24 kb

Euphoria longana Lam.

原著和名: リウガン科名: ムクロジ科 = Sapindaceae採集地: 鹿児島県 肝属郡 佐多町 伊座敷 (大隅 肝属郡 佐多町 伊座敷)採集日: 1957/7/10採集者: 萩庭丈壽整理番号: JH026103国立科学博物館整理番号: TNS-VS-97610

An Integrated Genome-Wide Systems Genetics Screen for Breast Cancer Metastasis Susceptibility Genes

<div><p>Metastasis remains the primary cause of patient morbidity and mortality in solid tumors and is due to the action of a large number of tumor-autonomous and non-autonomous factors. Here we report the results of a genome-wide integrated strategy to identify novel metastasis susceptibility candidate genes and molecular pathways in breast cancer metastasis. This analysis implicates a number of transcriptional regulators and suggests cell-mediated immunity is an important determinant. Moreover, the analysis identified novel or FDA-approved drugs as potentially useful for anti-metastatic therapy. Further explorations implementing this strategy may therefore provide a variety of information for clinical applications in the control and treatment of advanced neoplastic disease.</p></div

Identifying metastasis-associated genes using an integrated subtractive approach.

<p>A) Phylogenetic tree showing the inbred strains used in the original metastasis susceptibility screen and their phylogenetic relationship. Black labels indicate strains that were not significantly different from the original FVB/NJ MMTV-PyMT background. Red labels were strains that show significant reductions in pulmonary metastases. Underlined strains indicate strains sequenced by the Welcome Trust. The phylogenetic tree is adapted from Genetics (2010) v185 pgs 1081–1095 [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005989#pgen.1005989.ref006" target="_blank">6</a>]. B) Comparison of the metastatic capacity the MMTV-PyMT FVB/NJ, and NZB/B1NJ genotypes. The p value for the comparison between FVB/NJ and NZB/B1NJ metastatic capacity was calculated by ANOVA analysis corrected for multiple testing across the entire set of strains depicted in panel A. C) Schematic representation of the low stringency subtractive strategy to enrich for genes associated with metastatic progression. Grey peaks represent DNAse hypersensitivity sites.</p

Effect of Rosiglitazone on pulmonary metastasis.

<p>Surface metastasis counts for animals implanted with the highly metastatic mouse mammary tumor cell line 6DT1, treated with either vehicle (control) or Rosiglitazone. P values were calculated using a two-sided parametric t test. Scatterplots are shown with mean values with standard error of mean. All statistical calculations were performed using GraphPad Prism v. 6.01.</p

Metastasis-associated candidate genes predict outcome in human breast cancer.

<p>A) Distant metastasis-free survival analysis of the DMFS gene signatures (left panels) or the metastasis correlated gene signatures (right panels) on the GOBO data sets. Estrogen receptor status for each subset of patients is indicated above the Kaplan-Meier plots. B) Overall survival analysis of the mouse G7 metastasis-correlated gene signatures on the METABRIC patient data set. C) Performance of the G5 DMFS signature on the METABRIC validation data set after recalculation of gene weights on the METABRIC discovery data set.</p

Functional analysis of <i>Pvrl1</i> and <i>Zbtb16</i> validates the pDHS method.

<p>A) Gene lists were overlaid on the Chromosome 9 metastasis modifier locus to identify <i>Pvrl1</i> and <i>Zbtb16</i>. B) Results of the spontaneous pulmonary surface metastasis assays after orthotopic implantation of Mvt1 (left panel) mammary tumor cells with <i>Pvrl1</i> knocked down. P values represent the result of an ANOVA test after Dunnetts correction for multiple comparisons against the shControl data. C) Results of the spontaneous pulmonary surface metastasis assays after orthotopic implantation of Mvt1 cells over-expressing <i>Zbtb16</i>. The p value was calculated using a two-sided parametric t test. D) Metastasis incidence analysis of MMTV-PyMT animals either homozygous wild type (WT) or heterozygous knockout (+/-) for <i>Zbtb16</i>. The p value was calculated by a two-sided Chi-square test. E) Results of the spontaneous pulmonary surface metastasis assays after orthotopic implantation of wildtype Mvt1 cells into animals either homozygous wildtype (WT) or heterozygous knockout (+/-) for <i>Zbtb16</i>. The p value was calculated using a two-sided parametric t test. Scatterplots are shown with mean values with standard error of mean. All statistical calculations were performed using GraphPad Prism v. 6.01.</p