SIBLING STUDY OF AGE-RELATED MACULAR DEGENERATION

年龄相关性黄斑变性的兄弟研究

• 批准号: 7114852
• 负责人: MARGARET M DEANGELIS
• 金额: $ 61.73万
• 依托单位: MASSACHUSETTS EYE AND EAR INFIRMARY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7114852
• 关键词: apolipoprotein E; clinical research; developmental genetics; eye fundus photography; family genetics; genetic markers; genetic polymorphism; genetic susceptibility; human subject; linkage mapping; macular degeneration; molecular genetics; patient oriented research; siblings; smoking

DESCRIPTION (provided by applicant): We propose to recruit pairs of siblings for a molecular genetic search for genes having a role in the development of neovascular age-related macular degeneration (AMD). Two types of sibling pairs will be recruited, extremely discordant sibpairs and extremely concordant sibpairs. Extremely discordant sibpairs will be composed of one member, the index sib, with neovascular AMD, and the second member with few or no aging signs of the macula at the age at which the index sibling developed neovascular AMD. Extremely concordant sibpairs will be composed of two siblings with neovascular AMD. Leukocyte DNA will be purified from blood samples collected from these siblings. The sibpairs will form the basis for a genome-wide linkage study to search for chromosomal regions where the extremely discordant pairs, on average, share fewer alleles than expected by chance alone, and where the extremely concordant sibpairs, on average, share more alleles than expected. Chromosomal regions having these properties are likely to harbor AMD genes. In addition, candidate genes that may have a role in susceptibility to AMD, such as ABCA4 and apoE, will be analyzed by evaluating DNA sequence variations in those genes and looking for a correlation between any alleles and neovascular AMD. To our knowledge, a molecular genetics approach to finding genes for neovascular AMD based on extremely discordant and extremely concordant sibpairs has not been previously carried out by any other group of investigators. If successful, our work should provide substantial progress toward identifying the genetic causes of neovascular AMD, one of the leading causes of legal blindness among the elderly.

描述（由申请人提供）：我们建议招募成对的兄弟姐妹，以进行分子遗传搜索基因在新血管年龄相关的黄斑变性（AMD）中发挥作用。将招募两种类型的兄弟姐妹对，极度不和谐的sibpairs和极为一致的sibpairs。极度不一致的Sibpairs将由一个成员，索引SIB组成，具有新生血管AMD，第二个成员在索引同胞开发新血管AMD的年龄段的大黄斑迹象很少或没有衰老迹象。极度一致的sibpairs将由两个具有新生血管AMD的兄弟姐妹组成。白细胞DNA将从这些兄弟姐妹收集的血液样本中纯化。 Sibpairs将构成全基因组连锁研究的基础，以寻找染色体区域，在这些区域中，平均而言，极度不一致的对分子共享的等位基因少于仅一次机会，而在这种情况下，平均而言，平均而言非常一致的sibpairs共享等位基因比预期的要多。具有这些特性的染色体区域可能具有AMD基因。此外，将通过评估这些基因中的DNA序列变化并寻找任何等位基因与新等位基因AMD之间的相关性来分析可能在AMD易感性中起作用的候选基因，例如ABCA4和APOE。据我们所知，一种基于极度不一致和极端一致性的新血管AMD基因的分子遗传学方法以前尚未由任何其他研究人员进行。如果成功的话，我们的工作应该为确定新生血管AMD的遗传原因提供实质性进展，这是老年人中法律失明的主要原因之一。