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

超过145种有据可查的疾病和综合征表现出X连锁 传承 其中有一些疾病， 影响中枢神经系统，许多与精神 发育迟缓; 7种免疫性疾病; 12种主要 骨骼、结缔组织或皮肤表现; 4种类型的X- 相关耳聋和27个X相关眼病。 这些基因仅仅 这些疾病中的一小部分已经被确认。 X的两个区域- 染色体短臂编码多种眼病基因：近端 Xp 21-p11.2和Xp22.2-p22.1。 我们建议研究两个次区域， 近端Xp 21-p11.2，指定与X连锁视网膜炎相关的基因 色素沉着。 最近发现的一个保守序列区域， 具有连续基因的雄性BB中Xp 21缺失的断点 包括视网膜色素变性在内的综合征将被评估为 RP 3基因的候选人。 近端与远端之间的距离 BB缺失的断裂点与另一名男性SB的断裂点不同， 肉芽肿性疾病，麦克劳德表型和视网膜色素变性将 并搜索整个RP 3靶区域进行转录 单位以及指示基因的重排。 对于RP 2 区域，我们建议开发一个密集的银行保守序列DNA 从流式分选的X染色体的小插入文库中提取探针， 利用这些探针，连同参考标记，以完成 DXS 426之间区域的大片段、长距离限制性酶切图谱 DXS7 该图与DXS 255-DXS 426井段的图一起， 将为RP 2基因的系统搜索提供框架。 在 在其他研究中，我们将描述一个基因的优势表达， 在胎儿大脑中，来自染色体11 p区域的基因表达与 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.