Association Analysis of SNPs in Longevity Assurance Gen*

长寿保证 Gen* 中 SNP 的关联分析

• 批准号: 6949895
• 负责人: YOUSIN SUH
• 金额: $ 28.81万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6949895
• 关键词: DNA damage; European; Mexican Americans; animal tissue; clinical research; gene expression; gene targeting; genetic markers; genetic registry /resource /referral center; genetic screening; high throughput technology; human middle age (35-64); human old age (65+); human subject; linkage mapping; longevity; longitudinal human study; phenotype; quantitative trait loci; single nucleotide polymorphism

DESCRIPTION (provided by applicant): With the completion of the human genome project, attention is shifting towards individual genetic variation. Such variation, most of which consists of single nucleotide polymorphisms (SNPs), may account for a substantial portion of human individual phenotypic variation, including differences in aging-related characteristics. Especially important are SNPs that affect the function of genes in candidate longevity assurance pathways, since they could provide novel targets for the early detection and possible prevention of aging-related functional decline. Optimal study populations in this respect are those in which aging related phenotypes can be defined in terms of their progression from middle age onwards, rather than as snapshots in time. We hypothesize that genetic variation at loci involved in genome maintenance can be related to individual differences in the rate and severity of aging. To address this hypothesis, a systematic multidisciplinary study is proposed in which SNP haplotypes of about 100 genes in 5 genome maintenance pathways will be determined in individuals of an ongoing longitudinal study of 586 Mexican American (MA) and 428 European American (EA) (SALSA; San Antonio Longitudinal Study of Aging). Subsequent association analysis in conjunction with functional assays of allelic gene variants will provide insight into their biological significance. The results should lead to increased understanding of the role of genome maintenance in healthy aging and provide genetic markers to identify individuals at risk for specific aging related phenotypes. This will open up the possibility of targeted and personalized intervention strategies, ultimately leading to improved quality of life of the elderly population.

描述（由申请人提供）：随着人类基因组计划的完成，人们的注意力开始转向个体遗传变异。这种变异大部分由单核苷酸多态性（SNP）组成，可能解释了人类个体表型变异的很大一部分，包括衰老相关特征的差异。特别重要的是影响候选长寿保证途径中基因功能的单核苷酸多态性（SNP），因为它们可以为早期检测和可能预防与衰老相关的功能衰退提供新的靶标。在这方面，最佳的研究人群是那些可以根据从中年开始的进展来定义与衰老相关的表型的人群，而不是时间快照。我们假设参与基因组维护的基因座的遗传变异可能与衰老速度和严重程度的个体差异有关。为了解决这一假设，提出了一项系统的多学科研究，其中将在对 586 名墨西哥裔美国人 (MA) 和 428 名欧洲裔美国人 (EA) (SALSA) 进行的纵向研究的个体中确定 5 个基因组维护途径中约 100 个基因的 SNP 单倍型。 ；圣安东尼奥老龄化纵向研究）。随后的关联分析与等位基因变异的功能测定相结合将深入了解它们的生物学意义。这些结果应该有助于加深对基因组维护在健康衰老中的作用的理解，并提供遗传标记来识别具有特定衰老相关表型风险的个体。这将为有针对性和个性化的干预策略提供可能性，最终提高老年人口的生活质量。