DNA LINKAGE STUDIES OF DEGENERATIVE RETINAL DISEASES

描述：该项目的目的是确定类型和 常染色体显性遗传性视网膜色素变性的基因频率 (Adrp)来自美国西南部的一个种族多元化的人口 各州。ADRP是一组复杂的疾病，有多种遗传原因。 研究人员和其他人已经确定了至少8个基因或 导致这种情况的基因位点。然而，这不太可能是 导致ADRP的一整套基因；此外，病例的比例 由每种基因引起的疾病在很大程度上是未知的。这项提议的目的是 ADRP基因突变筛查和连锁检测的系统应用 患者和家属建立有用的数字估计和 在这个群体中潜在疾病基因的频率。 作为研究人员正在进行的研究的一部分，他们合作了 建立总部设在德克萨斯州达拉斯的西南眼科注册中心(SER)。 序列号为1。)德克萨斯州参加会议的视网膜专家名单， 俄克拉荷马州、阿肯色州和路易斯安那州谁治疗遗传性疾病患者 视网膜疾病和2.)编码的(非机密的)患者名单 这些临床医生看过的。目前，SER已经注册了超过15个 参与的视网膜专家和2100名患者，包括 如果使用adrp，大约有200人。从这个和其他来源来看， 调查人员已经确定了28个适合突变和 链接测试。在本提案的整个期间， 调查人员预计将识别出总共70至80个家庭 德克萨斯州和与之接壤的各州。突变筛查将由 伊利诺伊大学遗传性眼病分子诊断实验室 休斯敦。研究人员将检测视紫红质的突变， 利用单链构象的外周蛋白/RDS、ROM1等基因 分析和基因组测序。如果没有发现突变，那么对于 具有适合连锁排除的家系(7个或以上)的患者 可能提供信息的减数分裂)调查人员将测试是否存在关联 与已知的adrp基因座紧密连锁的微卫星标记或 相关的基因座。如果一个族足够大，可以包含链接(10或 更具潜在信息性的减数分裂)，如果先前的测试排除了 已知的基因座，然后研究人员将使用 利用一组微卫星标记进行全基因组连锁测试 以10厘米的间隔跨越人类基因组。最后，家庭展示 与候选基因的链接将被筛选出该基因的突变。 对引起ADRP的基因和突变的描述将是直接的 有利于患者的诊断和咨询，并将协助 合理规划诊断服务。此外，这一信息 将有助于更好地理解分子基础 这些疾病。最后，对引起疾病的基因进行表征 视网膜色素变性和相关情况应有助于设计 预防性治疗和治疗。

DESCRIPTION: The purpose of this project is to determine the types and frequencies of genes causing autosomal dominant retinitis pigmentosa (ADRP) in an ethnically-diverse population from the Southwestern United States. ADRP is a complex set of diseases with multiple genetic causes. The investigators and others have identified at least eight genes or gene loci causing this condition. However, it is unlikely that this is the complete set of genes causing ADRP; further, the fraction of cases caused by each gene is largely unknown. The intent of this proposal is to systematically apply mutation screening and linkage testing to ADRP patients and families to establish useful estimates of the numbers and frequencies of the underlying disease genes within this community. As part of the investigators' ongoing research they collaborated in establishing the Southwest Eye Registry (SER) based in Dallas, Texas. SER is 1.) a list of participating retinal specialists in Texas, Oklahoma, Arkansas and Louisiana who treat patients with inherited retinal diseases and 2.) an encoded (non-confidential) list of patients seen by these clinicians. Currently, SER has registered more than 15 participating retinal specialists and 2,100 patients, including approximately 200 with ADRP. From this and other sources the investigators have identified 28 families suitable for mutation and linkage testing. Throughout the period of this proposal the investigators anticipate identifying a total of 70 to 80 families within Texas and bordering states. Mutation screening will be conducted by the Laboratory for the Molecular Diagnosis of Inherited Eye Diseases at UT- Houston. The investigators will test for mutations in rhodopsin, peripherin/RDS, ROM1 and other genes using single strand conformational analysis and genomic sequencing. If mutations are not found, then for patients with families suitable for linkage exclusion (7 or more potentially informative meioses) the investigators will test for linkage to microsatellite markers tightly linked to the known ADRP loci or related loci. If a family is large enough for linkage inclusion (10 or more potentially informative meioses), and if prior testing excludes the known loci, then the investigators will test for new ADRP loci using genome-wide linkage testing with a panel of microsatellite markers that span the human genome at 10 cM intervals. Finally, families showing linkage to a candidate gene will be screened for mutations in this gene. Delineation of the genes and mutations causing ADRP will be of direct benefit to patients for diagnosis and counseling, and will assist in rational planning of diagnostic services. In addition, this information will contribute to a better understanding of the molecular bases of these diseases. Finally, characterization of the genes causing retinitis pigmentosa and related conditions should assist in design of preventive therapies and treatments.