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.

Public Health Relevance

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.

National Institute of Health (NIH)
National Human Genome Research Institute (NHGRI)
Research Project with Complex Structure Cooperative Agreement (UM1)
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Special Emphasis Panel (ZHG1)
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Fletcher, Colin F
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Baylor College of Medicine
Schools of Medicine
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