Association Analysis of SNPs in Longevity Assurance Genes

描述（由申请人提供）：随着人类基因组计划的完成，注意力正在转向个体遗传变异。这种变异，其中大部分由单核苷酸多态性（SNP）组成，可能占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。尤其重要的是影响候选长寿保障途径中基因功能的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下降提供新的靶点。在这方面，最佳的研究人群是那些与衰老相关的表型可以根据从中年开始的进展来定义的人群，而不是作为时间的快照。我们推测，基因组维护中涉及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，提出了一个系统的多学科研究，其中将在586名墨西哥裔美国人（MA）和428名欧洲裔美国人（EA）的正在进行的纵向研究（SALSA;圣安东尼奥老龄化纵向研究）的个体中确定5个基因组维持途径中约100个基因的SNP单倍型。随后的关联分析结合等位基因变异的功能测定，将提供深入了解其生物学意义。这些结果将有助于人们更好地理解基因组维持在健康老龄化中的作用，并提供遗传标记来识别特定衰老相关表型的风险个体。这将开辟有针对性和个性化的干预战略的可能性，最终导致改善老年人口的生活质量。

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.