Gene-SNP haplotype analysis of an aging population

老龄化人群的基因-SNP 单倍型分析

• 批准号: 6727074
• 负责人: YOUSIN SUH
• 金额: $ 7.3万
• 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: 2004-05-01 至 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6727074
• 关键词: aging; automated data processing; clinical research; computer assisted sequence analysis; computer system design /evaluation; data management; fluorescence; genetic mapping; genetic screening; genetic susceptibility; growth factor receptors; haploidy; human tissue; method development; mitochondrial DNA; musculoskeletal disorder; myostatin; polymerase chain reaction; single nucleotide polymorphism; two dimensional gel electrophoresis

With the entire human genome now almost completely decoded, attention is shifting towards individual genetic variation. Most of this variation consists of single nucleotide polymorphisms (SNPs), which can account for heritable inter-individual differences in, for example, disease susceptibility and response to medication. Aging is a major risk factor for most common human diseases. The identification of SNPs in candidate genes and the assessment of their potential functional impact on aging-related phenotypes will be important in assessing genetic components of aging, including exceptionally healthy aging. 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. The objective of this proposal is to further optimize a previously developed SNP discovery method, Two-Dimensional Gene Scanning (TDGS), to comprehensively analyze SNPs in multiple candidate genes in large, aging populations. The validity of this approach will be assessed through association analysis, in a case control manner, of all possible SNPhaplotypes of a selection of nuclear and mitochondrial genes involved in musculoskeletal function in a population of 226 Mexican American individuals of an ongoing longitudinal study of aging (San Antonio Longitudinal Study of Aging; SALSA). The results are expected to enrich the ongoing study with a genetic component for this particular phenotype and to demonstrate the validity of TDGS as a high-throughput platform to screen aging populations for all possible SNPs in hundreds and ultimately thousands of candidate genes (comprehensive candidate approach).

随着整个人类基因组现在几乎完全被破译，人们的注意力正在转移到个体基因变异上。大多数变异包括单核苷酸多态(SNPs)，它可以解释可遗传的个体间差异，例如，疾病易感性和对药物的反应。衰老是人类大多数常见疾病的主要风险因素。识别候选基因中的SNPs，并评估其对衰老相关表型的潜在功能影响，对于评估衰老的遗传成分，包括异常健康的衰老，将是重要的。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。这项建议的目的是 进一步优化先前开发的SNP发现方法--二维基因扫描(TDGS)，以在大规模老龄化人口中综合分析多个候选基因中的SNP。这种方法的有效性将通过病例对照的方式，通过对正在进行的老龄化纵向研究(圣安东尼奥老龄化纵向研究；SALSA)中226名墨西哥裔美国人中涉及肌肉骨骼功能的核和线粒体基因选择的所有可能的SNP单倍型的关联分析来评估。这些结果有望丰富正在进行的这一特定表型的遗传成分的研究，并证明TDGS作为一个高通量平台在数百个甚至最终数千个候选基因中筛选所有可能的SNP的有效性(综合候选法)。