GENETIC DISSECTION OF RESTRICTED REPETITIVE BEHAVIOR (RRB)

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 限制性重复行为RRB经常对受影响个人及其家人的日常生活造成重大干扰。尽管RRB具有重要的功能影响，但人们对RRB潜在的遗传机制总体上知之甚少。 Prader-Willi综合征PWS是一种罕见的遗传性疾病，由15q11-q13区域缺乏父系遗传基因引起。大多数PWS患者患有显著高水平的RRB。尽管PWS的分子机制已被很好地描述，但PWS表型的遗传基础尚不完全清楚。自闭症谱系障碍是一种比较常见的复杂遗传性疾病。有趣的是，15q11-q13区域也与ASD人群的子集有关。此外，ASD儿童和PWS儿童表现出相似的RRB水平，这表明PWS和ASD的RRB表型至少有一部分可能与共同的神经心理、神经递质或遗传起源有关。 在上述观察的基础上，我们提出了我们的中心工作假设，即15q11-q13含有共同的RRB危险基因等位基因。我们建议在15q11-q13区域研究RRB的遗传机制，以PWS和ASD作为RRB的聚集性障碍。如果在这些临床组中发现RRB的遗传基础，将为RRB的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.