GENETIC DISSECTION OF RESTRICTED REPETITIVE BEHAVIOR (RRB)

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Restricted repetitive behavior RRB often causes significant disruption to the daily lives of the affected individuals and their families. Despite its significant functional impact, little is known about underlying genetic mechanisms of RRB in general. Prader-Willi syndrome PWS is a rare genetic disorder caused by absence of paternally inherited genes in the 15q11-q13 region. Majority of PWS individuals suffer from significantly high levels of RRB. Despite well-characterized molecular mechanisms of PWS, genetic underpinnings for PWS phenotypes are not fully understood. Autism Spectrum Disorder ASD is a relatively common complex genetic disorder. Interestingly, the 15q11-q13 region has been also implicated in subset of ASD population. Furthermore, children with ASD and children with PWS show similar levels of RRB, suggesting at least a part of RRB phenotypes of both PWS and ASD may be associated with a common neuropsychological, neurotransmitter or genetic origin. Based on above observation, we developed our central working hypothesis that 15q11-q13 harbors common RRB risk genes alleles. We propose to study genetic mechanisms of RRB focusing on 15q11-q13 region, using PWS and ASD as paradigmatic disorders of RRB. If genetic underpinnings of RRB are identified in these clinical groups, it will provide valuable insights into the RRB pathogenesis, and help identifying novel targets for treatment of these chronic and disabling clinical conditions.