Association Analysis of SNPs in Longevity Assurance Genes

描述(申请人提供)：随着人类基因组计划的完成，人们的注意力正在转移到个人基因变异上。这种变异，其中大部分由单核苷酸多态(SNPs)组成，可能解释了人类个体表型变异的很大一部分，包括与年龄相关的特征的差异。尤其重要的是影响候选长寿保障途径中基因功能的SNPs，因为它们可以为早期发现和可能防止衰老相关的功能衰退提供新的靶点。在这方面，最佳研究群体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群体，而不是时间的快照。我们假设，基因组维持所涉及的基因座上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，其中将在正在进行的586名墨西哥裔美国人(MA)和428名欧洲裔美国人(EA)(SALSA；圣安东尼奥老龄化纵向研究)的个体中确定5条基因组维持途径中约100个基因的SNP单倍型。随后的关联分析与等位基因变异的功能分析将提供对其生物学意义的洞察。这一结果应该有助于加深对基因组维护在健康老龄化中的作用的理解，并提供遗传标记来识别特定衰老相关表型的风险个体。这将使有针对性和个性化的干预策略成为可能，最终提高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.