Discussion The epidermal growth factor receptor family is of tremen dous biological and clinical importance for many solid epithelial tumors

Specifically, significantly regulated genes were placed at the top or bottom of the list and ordered by descending or ascending fold changes, respectively. Less significantly regulated Discussion The epidermal growth factor receptor family is of tremen dous biological and clinical importance for many solid epithelial tumors genes were placed in the middle of the list and ordered by ascending or descending p values. Hierarchical clustering and heatmaps Hierarchical clustering was performed using the results of the GSEA. GO terms with the top ten Normalized Enrichment Scores were Discussion The epidermal growth factor receptor family is of tremen dous biological and clinical importance for many solid epithelial tumors selected and combined from both the upregulated and downregulated GO terms in each time point, compared to the 0 min treatment condition. Heatmaps were generated using the heat map. 2 function in the gplots package in R Discussion The epidermal growth factor receptor family is of tremen dous biological and clinical importance for many solid epithelial tumors with default parameters. Inputs for the heatmaps included nor malized GRO seq signals and NESs. For the latter, heatmaps comparing later to earlier time points were generated in a similar manner, but using different edgeR outputs for the comparisons. Background Genome wide mutagenesis and subsequent phenotype driven screening has been pivotal to a complete under standing of how complex biological processes operate in classical model organisms including flies, nematodes, and plants. The level of saturation in mutagenesis has been shown to be a critical parameter for this approach to determine all relevant genes involved in a biological function, without prior knowledge of the gene products. In mammalian model systems, much effort has been expended to saturate, i. e. to disclose all the genes involved in some specific biological pathways. However, the relatively large scale and labor intensity of experi ments have hampered the achievement of actual sat uration mutagenesis, especially for recessive traits that require biallelic mutations to manifest detectable phe notypes. To overcome these drawbacks, the haploid mouse embryonic stem cell system, in which a single hit mutation can directly lead to phenotypic changes without being compensated by the second copy of the gene, has been recently developed, and reviewed in. In this study, 86. 0% of ESCs remained haploid at the point of ENU treatment and the rest were diploid. In the diploidized ESCs, because either of the duplicated X chro mosomes could undergo X inactivation or chromosomal loss, an ENU induced mutation on the other allele of the X linked gene would immediately lead to a complete loss of function. This meant that, in the mixture of hap loid and diploid ESCs, X linked mutants would be more frequently obtained than autosomal recessive mutants. In the present study, prior to mutagenesis with ENU, we in troduced extra copies of human PIGA cDNA into the H129 2 haploid ESC line, but not into the HAP 1 haploid ESC line. As a result, X linked Piga mutants apparently dominated in the HAP 1 ESC population, whereas no Piga mutants, but instead various other autosomal mutants, appeared in the H129 2 ESC population. Pigg, Pign, and Pigq are known by their hypomorphic loss of function phenotypes. Consistently, a re cent ESC based mutagenesis study using the clustered regularly interspaced short palindromic repeats Cas system also screened for the resistance to toxin and failed to obtain Pigg, Pign, and Pigq mutants.