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解码，注意力正在转移到个体遗传​​变异。这种变化的大部分由单核苷酸多态性（SNP）组成，这些多态性（SNP）可以解释疾病易感性和对药物的反应中的个体间差异。衰老是大多数常见人类疾病的主要危险因素。候选基因中SNP的鉴定及其对与衰老相关的表型的潜在功能影响的评估对于评估衰老的遗传成分（包括异常健康的衰老）将很重要。在这方面，最佳研究人群是可以根据中期开始的发展来定义与衰老相关的表型的人群，而不是时间的快照。该提议的目的是 进一步优化了先前开发的SNP发现方法，即二维基因扫描（TDGS），以全面分析大型老龄化人群中多个候选基因中的SNP。这种方法的有效性将通过案例对照方式通过关联分析来评估，这些核心基因的所有可能的Snphaplotypes在226个墨西哥裔美国人的人群中，涉及肌肉骨骼功能的核和线粒体基因，该人群正在进行的衰老纵向研究（San antonio longitudinal longitudinal of Aging; Salssa）。预计该结果将通过该特定表型的遗传成分丰富正在进行的研究，并证明TDG作为一个高通量平台的有效性，用于为所有可能的SNP筛选成老化的人群，以数百和数千种候选基因（全面候选方法）。