HEREDITARY MACULAR DEGENERATION

遗传性黄斑变性

• 批准号: 2163968
• 负责人: KENT W SMALL
• 金额: $ 30.62万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-08-01 至 1998-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2163968
• 关键词: GABA receptor; artificial chromosomes; autosomal dominant trait; collagen; electrophysiology; family genetics; gene mutation; genetic disorder; genetic library; genotype; in situ hybridization; linkage mapping; macular degeneration; molecular cloning

The hereditary macular degenerations encompass a large number of poorly understood and confusing group of diseases which cause impairment of central vision. Some of these maculopathies have a classical Mendelian inheritance pattern and are individually uncommon while other maculopathies, such as age-related maculopathy (ARM), apparently are genetically influenced (but with non-Mendelian inheritance) and are very common thus representing a major public health dilemma. It is these less common maculopathies with classical inheritance patterns which are more amenable to powerful molecular genetic approaches and more likely to unlock the basic mysteries of macular function and dysfunction. The understanding and knowledge gained from these rarer disorders, can then be applied to more common diseases such as age-related maculopathy. The overall approach will be to fully characterize one macular specific disease, denoted MCDR1, clinically, electrophysiologically, psychophysically and molecularly and investigate this gene's role in ARM as well as other maculopathies. Patients affected with the MCDR1 phenotype have many similarities to ARM with the exception of the earlier age of onset. Because of these similarities, the full characterization of MCDR1 will reveal insights into ARM and macular specific function. The PI has recently clarified the clinical understanding, classification and gene localization of MCDR1. The next step will be to identify the mutation causing MCDR1, this will involve using in concert several new techniques such as chromosomal micro-dissection, enrichment cloning of new genetic markers and selective hybridization cloning. Then a genotype to phenotype correlation will be made. The MCDR1 gene will be used as a candidate gene for other genetically influenced macular disorders such as ARM, cone degeneration macular colobomata and similar incurable diseases.

遗传性黄斑变性包括大量的 理解和混淆一组疾病，这些疾病会导致 中心视觉。其中一些黄斑病变具有典型的孟德尔式 继承模式，并且个别地不常见，而其他 黄斑病变，如老年性黄斑病变(ARM)，显然是 受基因影响(但具有非孟德尔遗传)，并且非常 这很常见，因此是一个重大的公共卫生困境。正是这些较少 具有典型遗传模式的常见黄斑病变 服从强大的分子遗传学方法，更有可能 解开黄斑功能和功能障碍的基本谜团。这个 从这些罕见的疾病中获得的理解和知识，然后可以 适用于更常见的疾病，如老年性黄斑病变。 总的方法将是充分描述一个黄斑部特定的 疾病，表示为MCDR1，临床上，电生理上， 从心理生理和分子水平研究该基因在ARM中的作用 以及其他黄斑病变。受MCDR1影响的患者 表型与ARM有许多相似之处，除了更早的 发病年龄。由于这些相似之处， MCDR1将揭示手臂和黄斑的特定功能。《少年派》 最近澄清了临床认识、分类和基因 MCDR1的本地化。下一步将是确定突变 导致MCDR1，这将涉及到联合使用几种新技术 如染色体显微切割、新基因富集化克隆等 标记和选择杂交克隆。然后是从基因型到表型的转换 将会进行关联。MCDR1基因将被用作候选基因 用于其他受遗传影响的黄斑疾病，如手臂、视锥细胞 退行性黄斑裂孔和类似的不治之症。