Fragile X Syndrome: Banbury Conferences

描述（由申请人提供）：本提案要求支持班伯里脆性X染色体综合征（FXS）会议持续5年。包括首次会议在内，已经在纽约长岛冷泉港实验室的班伯里会议中心举行了六次这样的会议。我们提出了一系列的五个年度跨学科会议的基础和临床研究相关的脆性X综合征（FXS）。这些会议旨在汇集广泛的科学家，包括从事FXS工作的科学家和其他相关领域的科学家。另一个目标是向该地区介绍年轻科学家，包括女性和少数民族。脆性X综合征是智力迟钝的最常见遗传原因。它是由于FMR-1基因的5'非翻译启动子区域中三核苷酸重复的不稳定区域的扩增而产生的，导致胞嘧啶残基的超甲基化，并且通常导致基因的沉默。一些小鼠FMR-1敲除模型的综合征已经或即将成为可用的。脆性X智力低下蛋白（FMRP）的功能被认为是具有多种细胞功能的mRNA子集的转运和翻译调节。FMRP似乎在突触处响应于亲代谢性谷氨酸受体的激活而被翻译。在人类和基因敲除小鼠模型中，在几个脑区的总尺寸和突触的精细结构中可以看到这种疾病相对微妙的表型效应。正如班伯里会议已经明确（总结在第二节。我们对这种疾病的认识进展非常迅速。没有其他会议专门致力于FXS的基础和临床研究，与会者一致认为班伯里会议非常有价值。

DESCRIPTION (provided by applicant): This proposal requests support for a 5 year continuation of the Banbury Conferences on Fragile X syndrome (FXS). Including an initial conference, six such meetings have been held at Banbury Conference Center at Cold Spring Harbor Laboratory on Long Island NY. We propose a series of five annual interdisciplinary conferences on basic and clinical research relevant to fragile X syndrome (FXS). The conferences are intended to bring together a broad range of scientists, both those working on FXS and others in allied, relevant fields. Another goal is to introduce young scientists, including females and minorities, to the area. Fragile X syndrome is the most common inherited cause of mental retardation. It arises due to expansion of an unstable region of trinucleotide repeats in the 5' untranslated promoter region of the FMR-1 gene, causing hypermethylation of cytosine residues and, generally, silencing of the gene. A number of mouse FMR-1 knockout models for the syndrome have or are about to become available. The function of the fragile X mental retardation protein (FMRP) is believed to be the transport and translational regulation of a subset of mRNAs with a diverse set of cellular functions. FMRP appears to be translated at synapses in response to activation of metabotropic glutamate receptors. Relatively subtle phenotypic effects of the disorder are seen in the gross size of several brain regions and in the fine structure of synapses in humans and in the knockout mouse model. As the Banbury Conferences have made clear (summarized in Sec. C), advances in our knowledge of this disorder are occurring very rapidly. There is no other meeting devoted exclusively to basic and clinical research on FXS, and the participants consistently report the Banbury Conference to be extremely valuable.