SIBLING STUDY OF AGE-RELATED MACULAR DEGENERATION

年龄相关性黄斑变性的兄弟研究

• 批准号: 6799956
• 负责人: THADDEUS P DRYJA
• 金额: $ 48.81万
• 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/6799956
• 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）：我们建议招募一对兄弟姐妹进行分子遗传学研究，寻找在新生血管性年龄相关性黄斑变性（AMD）发展中起作用的基因。将招募两种类型的兄弟姐妹对，极其不和谐的兄弟姐妹对和极其和谐的兄弟姐妹对。极其不一致的同胞对将由一名成员（即患有新生血管性 AMD 的索引同胞）和第二名在索引同胞患上新生血管性 AMD 的年龄时黄斑很少或没有老化迹象的成员组成。极其一致的兄弟姐妹将由两个患有新生血管性 AMD 的兄弟姐妹组成。将从这些兄弟姐妹采集的血液样本中纯化白细胞 DNA。这些同胞对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，极端不一致的同胞对平均共享的等位基因比偶然预期的要少，而极其一致的同胞对平均共享的等位基因比偶然的预期多。预期的。具有这些特性的染色体区域可能含有 AMD 基因。此外，将通过评估这些基因中的 DNA 序列变异并寻找任何等位基因与新生血管性 AMD 之间的相关性来分析可能在 AMD 易感性中发挥作用的候选基因，例如 ABCA4 和 apoE。据我们所知，之前任何其他研究小组都没有采用过基于极其不一致和极其一致的同胞对来寻找新生血管性 AMD 基因的分子遗传学方法。如果成功，我们的工作将在确定新生血管性 AMD 的遗传原因方面取得实质性进展，新生血管性 AMD 是老年人法定失明的主要原因之一。