Understanding The Developmental Effects Of A Non Coding Mutation Associated With Schizophrenia Could Significantly Advance The Field

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This is the first submission of R21 by an Early Stage Investigator. The comments for the application were received in August, 2015. All reviewers’ comments were very helpful. I thank them for the time and thought they put into the reviews. We have made significant effort to address the reviewers’ comments and suggestions, providing new preliminary data for this proposal as following.
I appreciate the reviewers for their overall enthusiasm for this proposal: 1) “Understanding the developmental effects of a non-coding intronic mutation associated with schizophrenia could significantly advance the field.” 2) “The investigator has a strong track record of productivity.” 3) “Strengths include the excellent preliminary data, the interesting gene target, live cell imaging studies, use of human iPSCs, and the high risk / high reward.” 4) “…introduce human iPSC cells carrying risk alleles into the developing mouse cortex is particularly strong.” 5) “The applicant is a young investigator, well-trained for the work he proposes. He will have two highly experienced consultants.” 6) “…this application breaks away from the crowd somewhat in investigating an allele that lies in an intron of the risk gene.” However, some concerns arise on “the rationale that intronic mutation in ZNF804a is the causal variant, the electroporation approach and the transplantation of iPSCs into mice” as shown in the summary paragraph. We will address these comments point-by-point for each reviewer below.…

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