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: 6890339
• 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/6890339
• 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解码，人们的注意力正在转向个体遗传变异。这种变异大部分由单核苷酸多态性 (SNP) 组成，它可以解释遗传性的个体间差异，例如疾病易感性和对药物的反应。衰老是大多数常见人类疾病的主要危险因素。识别候选基因中的单核苷酸多态性（SNP）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）非常重要。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。该提案的目的是 进一步优化先前开发的SNP发现方法——二维基因扫描（TDGS），以全面分析大型老龄化人群中多个候选基因的SNP。该方法的有效性将通过关联分析来评估，以病例对照的方式，对参与一项正在进行的衰老纵向研究的 226 名墨西哥裔美国人的肌肉骨骼功能所选择的核和线粒体基因的所有可能的 SNPhaplotypes 进行评估。圣安东尼奥老龄化纵向研究；SALSA）。预计结果将丰富正在进行的针对这种特定表型的遗传成分的研究，并证明 TDGS 作为高通量平台的有效性，用于筛选老龄化人群中数百个甚至数千个候选基因中所有可能的 SNP（综合候选方法） ）。