CHROMOSOMAL MAPPING--X-LINKED EYE GENES AND A BRAIN GENE

超过145种有充分记录的疾病和综合征显示出X-连锁 继承。在这些疾病中，有一些主要是 影响中枢神经系统，许多与精神疾病有关 发育迟缓；7种免疫紊乱；12种综合征，以 骨骼、结缔组织或皮肤表现；4种X- 遗传性耳聋和27种X-连锁眼病。仅有的潜在基因 这些疾病中的一小部分已经被确认。X的两个方面- 多发性眼病的染色体短臂编码基因：近端 Xp21-p11.2和Xp22.2-p22.1。我们建议研究以下两个亚区 近端Xp21-p11.2，指定与X连锁视网膜炎相关的基因 着色剂。最近发现的一个保守序列区域 具有邻接基因的男性BB中Xp21缺失的断裂点 包括视网膜色素变性在内的综合征将被评估为 RP3基因的候选人。近端之间的距离 另一名慢性男性SB的BB缺失的断裂点 肉芽肿性疾病、McLeod表型和视网膜色素变性 并搜索整个RP3靶区以进行转录 单位以及指示基因的重排。对于RP2 区域，我们建议建立一个高密度的保守序列DNA库 来自流动分类X染色体的小插入文库的探针 利用这些探针与参考标记一起完成 DXS426之间区域的大片段、长距离限制图 和DXS7。该映射与DXS255-DXS426间隔的映射一起， 将为系统地寻找RP2基因提供一个框架。在……里面 在其他研究中，我们将描述一种主要表达的基因 在胎儿大脑中，来自染色体11p的一个相关区域 精神发育迟滞。

More than 145 well documented diseases and syndromes exhibit X-linked inheritance. Among these are a number of disorders which predominantly affect the central nervous system, many associated with mental retardation; 7 immunological disorders; 12 syndromes with predominant skeletal, connective tissue or cutaneous manifestations; 4 types of X- linked deafness and 27 X-linked eye disorders. The genes underlying only a fraction of these diseases have been identified. Two areas of the X- chromosome short arm encode genes for multiple eye disorders: proximal Xp21-p11.2 and Xp22.2-p22.1. We propose to study two subregions of proximal Xp21-p11.2 that specify genes involved in X-linked retinitis pigmentosa. A recently identified conserved sequence region near the breakpoint of an Xp21 deletion in the male BB with a contiguous gene syndrome that included retinitis pigmentosa will be evaluated as a candidate for the RP3 gene. The distance separating the proximal breakpoint of the BB deletion from that of another male, SB, with chronic granulomatous disease, the McLeod phenotype and retinitis pigmentosa will be determined and the entire RP3 target region searched for transcription units as well as rearrangements indicative of the gene. For the RP2 region, we propose to develop a dense bank of conserved sequence DNA probes from a small insert library of flow sorted X-chromosomes and to utilize these probes, together with reference markers, to complete a large fragment, long range restriction map of the region between DXS426 and DXS7. This map, together with that for the DXS255-DXS426 interval, will provide a framework for a systematic search for the RP2 gene. In other studies, we will characterize a gene with predominant expression in fetal brain that is derived from a region of chromosome 11p implicated in mental retardation.