This supplement describes the development of a robust yet rapid phenotyping pipeline to annotate lethality and phenotype information from essential genes. Using this approach, we can rapidly analyze a large number of lines, since F0 embryos will be analyzed directly, rather than establishing founder lines and expanding cohorts for embryo/adult animal production. The analysis of F0 embryos has been published previously by our colleagues, supporting the feasibility of this approach. With implementation of the new pipeline, we predict that each KOMP2 center can annotate 200 genes in the one-year time period of the supplement for a total of 600 new genes annotated. This pace would roughly double our rate of phenotype discovery for this year.
The current KOMP2 workflow does not enable phenotype data to be captured if the null mutation results in dominant lethality and founder mice are not produced. This subset of haplo-essential genes is likely to be 15% of the genome and highly enriched in human disease. Here we propose an efficient and low cost pipeline to annotate the phenotypes of haplo-essential genes, providing key data for researchers and clinicians with an accelerated rate of phenotype discovery compared with our current pipelines.
|Szwarc, Maria M; Kommagani, Ramakrishna; Putluri, Vasanta et al. (2018) Steroid Receptor Coactivator-2 Controls the Pentose Phosphate Pathway through RPIA in Human Endometrial Cancer Cells. Sci Rep 8:13134|
|Singh, Ravi K; Kolonin, Arseniy M; Fiorotto, Marta L et al. (2018) Rbfox-Splicing Factors Maintain Skeletal Muscle Mass by Regulating Calpain3 and Proteostasis. Cell Rep 24:197-208|
|Lanza, Denise G; Gaspero, Angelina; Lorenzo, Isabel et al. (2018) Comparative analysis of single-stranded DNA donors to generate conditional null mouse alleles. BMC Biol 16:69|
|Rozman, Jan; Rathkolb, Birgit; Oestereicher, Manuela A et al. (2018) Identification of genetic elements in metabolism by high-throughput mouse phenotyping. Nat Commun 9:288|
|Raghunathan, Suchi; Reynolds, Corey L; Schwartz, Robert J et al. (2018) C.B-17 SCID mice develop epicardial calcinosis with unaltered cardiac function. Fundam Clin Pharmacol :|
|Codner, Gemma F; Mianné, Joffrey; Caulder, Adam et al. (2018) Application of long single-stranded DNA donors in genome editing: generation and validation of mouse mutants. BMC Biol 16:70|
|Albrecht, Nicholas E; Alevy, Jonathan; Jiang, Danye et al. (2018) Rapid and Integrative Discovery of Retina Regulatory Molecules. Cell Rep 24:2506-2519|
|Moore, Bret A; Leonard, Brian C; Sebbag, Lionel et al. (2018) Identification of genes required for eye development by high-throughput screening of mouse knockouts. Commun Biol 1:236|
|Tanner, Mark R; Pennington, Michael W; Chamberlain, Brayden H et al. (2018) Targeting KCa1.1 Channels with a Scorpion Venom Peptide for the Therapy of Rat Models of Rheumatoid Arthritis. J Pharmacol Exp Ther 365:227-236|
|Morriss, Ginny R; Rajapakshe, Kimal; Huang, Shixia et al. (2018) Mechanisms of skeletal muscle wasting in a mouse model for myotonic dystrophy type 1. Hum Mol Genet 27:2789-2804|
Showing the most recent 10 out of 20 publications