2001 CAG Triplet Repeat Disorders

本申请是为2001年7月15日至20日在美国马萨诸塞州蒙特霍利奥克学院举行的2001年关于CAG三联体重复障碍的戈登研究会议申请资金。两大类遗传性神经系统疾病最近被确定为不稳定三联体重复疾病。他们的发现代表了遗传学一套新原理的基础。一类疾病包括脆性X染色体、强直性肌营养不良和弗里德赖希共济失调。患有这些疾病的患者都表现出DNA基因组的非编码序列中三联体重复的扩增。相反，另一组神经系统疾病在基因组的编码部分中表现出扩展的三联体重复序列（编码CAG碱基），导致多聚谷氨酰胺束。后一组包括亨廷顿病、脊髓小脑共济失调1、2、3、6和7、脊髓延髓肌肉萎缩和齿状核红核苍白球-路易体萎缩。这些疾病导致大脑和脊髓中神经元的选择性损失，每种疾病的解剖分布不同。虽然遗传缺陷已经确定，但在每种情况下，突变基因如何产生特定的发病过程，以及这如何导致特征性的解剖学变化模式，仍有待阐明。这些突变基因的鉴定为许多受严重遗传疾病影响的人带来了希望。然而，在开发新的治疗方法之前，有必要更好地了解疾病的过程。这需要多学科的研究努力，从果蝇遗传学到临床神经学和神经病理学等不同专业的科学家之间的合作项目。这次关于CAG三联重复障碍的会议将聚集年轻和资深的关键科学家，他们将在科学前沿发表发人深省的演讲。为了与戈登研究会议的形式保持一致，将有大量的时间分配给由同行领导的结构化讨论和非正式讨论，并将大量的时间分配给由同行领导的结构化讨论和非正式讨论和社交互动。特别强调对青年科学家的培训和指导，并将时间用于职业问题。将鼓励所有与会者（发言者和讨论者除外）展示海报。在选择参与者时，还将优先考虑妇女、少数民族和残疾人

This application is to request funding for the 2001 Gordon Research Conference on CAG triplet repeat disorders to be held in Mount Holyoke College, MA, USA, July 15-20, 2001. Two major groups of genetic neurological disorders were recently identified as unstable triplet repeat diseases. Their discovery represents the foundation of a new set of principles in genetics. One group of diseases includes fragile X, myotonic dystrophy and Friedreich's ataxia. Patients with these disorders all exhibit an expansion of triplet repeats in a non-coding sequence of the DNA genome. In the contrast, the other group of neurologic disorders exhibit expanded triplet repeats (coding for CAG bases) in the coding part of the genome, resulting in a polyglutamine tract. This latter group includes Huntington's disease, spino-cerebellar ataxia 1, 2, 3, 6 and 7, spinobulbar muscular atrophy and dentato-rubral pallido-luysian atrophy. These disorders results in a selective loss of neurons in the brain and spinal cord, with a different anatomical distribution in each disease. Although the genetic defects are established, it remains to be elucidated how the mutant gene in each case generates the specific pathogenetic process and how this leads to a characteristic anatomical pattern of changes. The identification of these mutant genes raises hopes for many affected by severe genetic disease. However, before development of novel therapies can be expected, it is necessary to better understand the disease processes. This requires a multi-disciplinary research effort with collaborative projects between scientists from diverse specialties ranging from fruit fly genetics to clinical neurology and neuropathology. This conference on CAG triplet repeat disorders will gather both young and senior, key scientists who will present provoking lectures on the cutting-edge of science. In keeping with the Gordon Research Conference format, there will be generous time allocated to both structured discussions led by peers and for informal discussions and social generous time allocated to both structured discussions led by peers and for informal discussions and social interaction. Strong emphasis is placed on training and mentoring of young scientists and time is also devoted to career issues. All participants (except speakers and discussants) will be encouraged to present posters. When participants are selected there will also be priority given to women, minorities, and persons with disabilities