Genetic Epidemiology of Telomere Length in the Amish

阿米什人端粒长度的遗传流行病学

• 批准号: 7238648
• 负责人: WEN-CHI HSUEH
• 金额: $ 29.59万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 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 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7238648
• 关键词: Age; Aging; Amish; Arts; Biological; Biological Markers; Candidate Disease Gene; Cardiovascular Diseases; Cardiovascular system; Cell Aging; Chromosome Mapping; Chromosomes; Clinical; Cohort Studies; DNA; DNA biosynthesis; Data; Development; Disease; Environmental Risk Factor; Family; Family Study; Founder Generation; Funding; Genes; Genetic; Genetic Determinism; Genetic Markers; Genome; Genome Scan; Genotype; Health; Heritability; Human; Individual; Inflammation; Intervention Studies; Investigation; Knowledge; Length; Life; Link; Longevity; Measurement; Measures; Metabolic syndrome; Methods; Non-Insulin-Dependent Diabetes Mellitus; Osteoporosis; Outcome; Participant; Pathway interactions; Phenotype; Population; Population Study; Recruitment Activity; Regenerative Medicine; Regulation; Research Design; Research Proposals; Risk Factors; Scanning; Services; Short Tandem Repeat; Somatic Cell; Spouses; Stem cells; Study Subject; Tandem Repeat Sequences; Telomere Shortening; Therapeutic; Tissue Transplantation; Variant; age related; base; bone; calcification; cardiovascular disorder risk; genetic epidemiology; genome-wide linkage; healthy aging; insight; longevity gene; sex; telomere; trait

DESCRIPTION(provided by applicant): Telomere shortening has been causally linked to cellular senescence in different species, and in humans, telomere shortening has been associated with aging and poorer survival. In addition, prior genetic studies suggest that telomere length is heritable. We hypothesize that telomere shortening is associated with aging, and it is variable and heritable in the Old Order Amish (OOA). The primary objectives of this research proposal are three-fold: (1) to examine whether shorter telomere lengths (TLs) are positively associated with aging at a population level; (2) to characterize genetic epidemiology of TLs and, (3) to identify genetic markers associated or linked to TLs. Telomere lengths will be measured using a newly developed and validated quantitative-PCR method. Information on TL measurements and age-related phenotypes will be obtained from 1,300 individuals in ongoing studies in the OOA. These subjects, who are participants in other studies, have been or will be extensively characterized with regards to traits related to cardiovascular diseases, metabolic syndrome, osteoporosis, and inflammation. Furthermore, data from a 5-cM genome-scan are already available in 1,000 study participants, which allow us to conduct a genome-wide linkage study searching for loci related to TL. No additional funding will be required for phenotypic characterization of age-related traits or genotyping for genome-wise scan in this proposed study. This proposed study will hopefully provide Insight into the association between telomere length and aging in humans and help in evaluating whether telomere length can be used as a biological marker of aging. Any positive findings will encourage further investigation into the biological relationship between TLs and aging. Unraveling the genetic pathways involved in the regulation of telomere length will have important and farreaching implications in understanding many aspects of human health and diseases. Such knowledge may also aid in the development of regenerative medicine, cultured tissue transplantation, and stem cell therapeutics.

描述（由申请人提供）：端粒缩短与不同物种的细胞衰老有关，在人类中，端粒缩短与衰老和较差的生存有关。此外，先前的遗传研究表明端粒长度是可遗传的。我们假设端粒缩短与衰老有关，并且在旧顺序Amish（OOA）上是可变和可遗传的。这项研究建议的主要目标是三倍：（1）检查较短的端粒长度（TLS）是否与人口水平的衰老呈正相关； （2）表征TLS的遗传流行病学和（3），以识别与TLS相关或相关的遗传标记。 端粒长度将使用新开发和验证的定量PCR方法进行测量。在OOA正在进行的研究中，将从1,300个人获得有关TL测量和与年龄相关的表型的信息。这些受试者是其他研究的参与者，已经或将广泛地描述与与心血管疾病，代谢综合征，骨质疏松症和炎症相关的特征。此外，1000名研究参与者已经提供了5 cm基因组can的数据，这使我们能够进行全基因组的联系研究，以搜索与TL相关的基因座。在这项拟议的研究中，对于年龄相关性状或基因组扫描的基因分型的表型表征不需要额外的资金。 这项拟议的研究有望提供有关人类端粒长度与衰老之间关联的见解，并有助于评估端粒长度是否可以用作衰老的生物学标志。任何积极的发现都将鼓励进一步研究TLS与衰老之间的生物学关系。阐明端粒长度调节所涉及的遗传途径将对理解人类健康和疾病的许多方面具有重要意义。这种知识还可以有助于开发再生医学，培养的组织移植和干细胞疗法。