The main objective ofthe RNA Sequencing Core (RSC) is to provide users with efficient and high quality access to cutting-edge sequencing technologies. These sequencing technologies will be used by all members of this U54-proposal, and made available to other U54-centers. Importantly, all members of this U54 are relying on access to these technologies to achieve their project goals. By centralizing sequencing at the RSC, sequencing will be performed at a lower cost and with greater efficiency that would be possible for individual users. The RSC will use high-throughput next-generation sequencing in two different applications. The first application will be to quantify the abundance of all messenger RNAs (mRNA) in a sample, this information is useful in describing the overall physiological state of a cell because all proteins are encoded by mRNAs. The second application will be to identify all small RNAs in a sample; small RNAs regulate the production of proteins by interacting with mRNAs. RSC staff will validate RNA sample quality, convert the RNA into a form suitable for high-throughput sequencing, and either perform sequencing on instruments within the RSC or perform the sequencing at the Cornell Genomics Facility. Cornell University will provide space for the RSC in the Biotechnology building, which also houses the Cornell Genomics Facility. Dr. Grimson, the RSC director, has his office within the Biotechnology building. The computational analysis of sequencing data often represents a bottleneck for the adoption of these technologies by biologists and physician-scientists. The RSC will remove this impediment by providing professional computational support to users, and working with users to make optimal use of their data. The RSC will sequence human samples, including samples from patients with fertility problems, and from mouse samples, including those containing mutations that perturb germline and reproductive functions. Together, the sequencing data will generate critical insights into reproductive biology in mammals, with direct relevance to human reproductive health. As an additional benefit ofthe RSC, the centralizing of sequencing and analysis will further facilitate synergism between all members of this U54, and with other U54 centers ofthe SCCPIR.