CANDIDATE GENES IN HEREDITARY EYE DISEASES

在儿童年龄组中，至少50%的新发法定失明病例 美国可以归因于遗传原因，但我们的理解 眼科疾病的遗传基础仍然非常有限。此外， 临床异质性出现在看起来相同和/或相同的疾病中 具有相同的名字，但由不止一种基因异常引起。 因此，有必要对大量家庭进行评估以 确定可能的基因。导致分离的基因的正常功能 眼部疾病或有明显的眼部症状，如常染色体 显性先天性白内障和视网膜退行性变尚不清楚。这个 这项研究提案的主要焦点是使用重组DNA技术 绘制和识别导致遗传性眼病的基因。我们计划确认 或排除眼睛特定识别的RFLP之间的共隔离 各种遗传性眼病的探针和基因；我们特别 计划研究常染色体显性遗传性先天性白内障和视网膜 堕落的人。如果排除了种族隔离，标准的连锁分析 将会被执行。在眼科疾病的情况下，染色体 已通过先前的连锁分析试探性地进行了赋值 与编码疾病的基因非常接近，特别是候选基因 将使用探头来识别RFLP。我们还计划绘制所有可用的地图 利用体细胞杂交和原位杂交的眼睛特异DNA探针 杂交。拟议研究收集的信息将有所改善 我们对参与各种疾病的基因的理解，他们的 正常功能，以及这些功能如何因突变而改变。是这样的 信息将改进疾病分类并确定基因 表型明显相似的疾病之间的异质性。这个 提高遗传咨询的准确性。此外， 了解突变基因的功能可能有助于深入了解 疾病的发病机制，并为延迟和/或预防提供线索 突变基因的表达。如果出现以下情况，这一点就变得尤为重要 有多个遗传位点导致相同或相似的表型 功能。管理和改变不同突变体表达的方法 对于每个基因座来说，基因可能是不同的，也是特定的。

At least 50% of new cases of legal blindness in the pediatric age group of the United States can be attributed to genetic causes but our understanding of the genetic basis of ocular disease is still very limited. Furthermore, clinical heterogeneity occurs in disease which appear to be the same and/or carry the same name but are caused by more than one genetic abnormality. Thus, it will be necessary to evaluate a large number of families to identify putative genes. The normal function of genes which cause isolated ocular diseases or have significant ocular manifestations such as autosomal dominant congenital cataracts and retinal degenerations is unknown. The major focus of this research proposal is to use recombinant DNA techniques to map and identify genes causing genetic eye diseases. We plan to confirm or exclude cosegregation between the RFLPs identified by eye-specific probes and the genes for various inherited eye diseases; we specifically plan to study autosomal dominant congenital cataracts and retinal degenerations. If cosegregation is excluded, standard linkage analysis will be performed. In the case of an eye disease for which a chromosomal assignment has been tentatively made by prior linkage analysis, probes in close proximity to the gene encoding the disease, especially candidate gene probes will be used to identify RFLPs. We also plan to map all available eye-specific DNA probes using somatic cell hybridization, and in situ hybridization. Information gathered by the proposed studies will improve our understanding of the genes involved in the various disorders, their normal functions, and how these functions are altered by mutations. Such information will improve disease classification and will identify genetic heterogeneity among disorders of apparently similar phenotype. The accuracy of genetic counseling will be enhanced. Furthermore, understanding the function of the mutated genes may provide insight into the pathogenesis of the disorders and provide clues to delay and/or prevent the expression of the mutated gene. This becomes particularly important if there are multiple genetic loci causing the same or similar phenotypic features. The means to manage and alter the expression of different mutant genes probably would be different and specific for each locus.