The Seattle-Davis Fragile X Research Center was formed in 2003 to bring together clinical and laboratory researchers at the University of Washington, University of California-Davis, and the Hutchinson Cancer Center whose interests focus on fragile X syndrome. Significant progress has been made in four areas of the Center: recognition and characterization of a new FMR1 disease, fragile X associated tremor ataxia (FXTAS); discovery of a new gene that overlaps with FMR1, encoding an antisense transcript with possible regulatory roles; development of critical new methods for epigenetic analysis to understand the variable inactivation of FMR1; and the establishment of a Patient Recruitment and Evaluation Core that has functioned well to the benefit of patients, families, and researchers. ? ? Progress during the previous program period has encouraged the investigators to expand their research and clinical expertise for this competitive renewal application. They are joined in this application by three scientists who represent fundamental areas in fragile X and FXTAS research: Dr. David Morris, University of Washington, who brings expertise in RNA processing and sliced isoforms of FMRP; Dr. Elizabeth Berry-Kravis, who is a leading fragile X clinical and research physician working at Rush University Medical Center; and Dr. William Greenough, University of Illinois, who brings expert skill and accomplishment in basic and fragile X neurobiology. ? ? The expanded group plans clinical and laboratory research projects enhanced by collaborations internal and external to the Research Center. The remarkable success of the Patient Recruitment and Evaluation Core has led to the proposition of a multi-institutional project on new-born screening for pre- and full mutations that will clarify the developmental consequences of the mutations in babies, and the involvement of fragile X-related disease in families. In addition, the functional and structural roles of the antisense transcript at FMR1 will be explored, including possible molecular-clinical correlations with FXTAS; a broad collaboration will identify functional specializations among the various protein isoforms of FMR protein; another collaboration addresses phenotypic consequences of restoring partial function of FMRP across regional, temporal, and molecular scales; and NIH-approved lines of human embryonic stem cells will be used to help understand early developmental processes leading the variable epigenetic inactivation of FMR1. ? ? ?
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