GENETIC DISSECTION OF RESTRICTED REPETITIVE BEHAVIOR (RRB)

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 限制性重复行为RRB通常会对受影响的个人及其家庭的日常生活造成严重干扰。尽管其重要的功能影响，很少有人知道RRB的遗传机制。 Prader-Willi综合征PWS是一种罕见的遗传性疾病，由15 q11-q13区域缺乏父系遗传基因引起。大多数PWS个体患有显著高水平的RRB。尽管PWS的分子机制已得到很好的表征，但PWS表型的遗传基础尚未完全了解。自闭症谱系障碍ASD是一种相对常见的复杂遗传性疾病。有趣的是，15 q11-q13区域也与ASD人群的子集有关。 此外，患有ASD的儿童和患有PWS的儿童显示出相似的RRB水平，这表明PWS和ASD的至少一部分RRB表型可能与共同的神经心理学、神经递质或遗传起源相关。 基于上述观察，我们提出了我们的中心工作假设，即15 q11-q13具有共同的RRB风险基因等位基因。我们建议以PWS和ASD为RRB的典型疾病，从15 q11-q13区域研究RRB的遗传机制。如果在这些临床组中确定RRB的遗传基础，将为RRB发病机制提供有价值的见解，并有助于确定治疗这些慢性和致残性临床疾病的新靶点。

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.