This Core will focus on identifying the genetic lesions underlying repro mutations. This is essential for understanding the molecular basis of infertility phenotypes and enhances the overall value of the resource to the community. Previously, this task was a distributed effort, but in the review of the previous submission of this renewal, the reviewers made a sensible recommendation that a Core focused on positional cloning would better facilitate the achievement of these goals. We agree. The new Core B will be directed by Dr. Schimenti and co-directed by Dr. Handel. Its operation as a distinct Core will formalize the model that we already use successfully, one which takes advantage of respective expertise and resources. First, Dr. Schimenti has extensive experience in both fine mapping and positional cloning; his lab has cloned 22 chemically-induced mutations in various projects. Second, ReproGenomics colony maintenance runs smoothly at The Jackson Laboratory (JAX), where Dr. Handel supervises the breeding and stock maintenance aspects required for fine mapping and positional cloning. We look forward to the key role that the new external advisory committee will play in prioritizing activities of this Core. Initially, Core B will focus on cloning the mutations that are the focus of Projects II and III. Subsequently, we will positionally clone selected newly generated mutations - those that appear to be novel or of special interest to the overall community by virtue of map position or phenotype (determined by Core A). As representatives of the reproductive biology community, the advisory committee will have major input into decisions prioritizing which mutations to clone. Another factor that will be considered in setting priorities is whether there are external scientists interested in a particular repro mutant, but who lack the experience or resources to pursue the cloning on their own; examples of these from the previous funding period are repro27 and repro32, where the causative gene was identified by end users as a result of our collaboration in fine mapping. We will continue such collaborations under the auspices of Core B.
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