Studies of Rare Genetic Variation in the Isolated Population of Sardinia

撒丁岛隔离种群罕见遗传变异的研究

• 批准号: 8930263
• 负责人: Goncalo Abecasis
• 金额: $ 160万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-01-15 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8930263
• 关键词: Aging; Biology; Blood; Blood Pressure; Cardiovascular system; Chromosome Mapping; Code; Complement; Complex; Data; Development; Disease; Evaluation; Face; Family; Founder Generation; Frequencies; Functional RNA; Generations; Genetic; Genetic Polymorphism; Genetic Population Study; Genetic Variation; Genome; Genotype; Haplotypes; Health; High-Throughput Nucleotide Sequencing; Human; Human Genetics; Imagery; Individual; Island; Italy; Laboratories; Measurement; Meta-Analysis; Methods; Modeling; Molecular; Obesity; Outcome; Population; Protocols documentation; Recruitment Activity; Relative (related person); Research; Research Design; Risk Factors; Role; SNP genotyping; Sampling; Sampling Studies; Sardinia; Sequence Analysis; Site; Technology; Testing; Variant; age related; analytical method; base; blood lipid; cardiovascular disorder risk; cardiovascular risk factor; deep sequencing; design; genetic analysis; genetic pedigree; genetic variant; genome sequencing; genome wide association study; heart disease risk; high throughput technology; insertion/deletion mutation; insight; interest; modifiable risk; next generation sequencing; rare variant; research study; success; tool; trait

DESCRIPTION (provided by applicant): Next generation sequencing is gradually changing the face of human genetic studies. Instead of being largely confined to the analysis of common SNPs shared across many populations and amenable to microarray genotyping, genome-wide studies can now examine a wider range of genetic variants - including more diverse types of variation (such as insertion-deletion polymorphisms), variants specific to particular samples or populations, and rare and low frequency variants. Here, we request continued support for our genetic analysis of aging related traits - with a focus on cardiovascular risk factors - in the isolated population from the island of Sardinia, Italy. Over the next several years, we will use next-generation sequencing technology and high-throughput genotyping to study the relationship between rare genetic variation and key cardiovascular risk factors in a family sample containing ~6,000 individuals (and >30,000 close relative pairs) recruited in the Lanusei valley. As part of our planned experiments, we will evaluate problems related to the selection of samples for sequencing, the design of sequencing experiments and protocols, the analysis and curation of the resulting sequence data, and - finally - association analyses that connect the resulting variants to relevant biomedical traits. Individuals being studies are part of a longitudial study of aging and have been characterized for cardiovascular traits and outcomes, including multiple measurements of key traits such as blood lipid levels and blood pressure. We have previously studied this sample to identify common genetic variants that are associated with these cardiovascular traits and that also contribute to the risk of heart disease and obesity. Our proposed experimental plan presents a unique opportunity to evaluate the role of rare variation in this unique sample. We expect that these studies will result in experimental strategies and analysis tools that will be readily deployable by many laboratories to study the genomes of many other individuals and further our understanding of the genetics and biology of many different traits and conditions.

描述（由申请人提供）：下一代测序正在逐渐改变人类基因研究的面貌。而不是很大程度上局限于分析共同的snp在许多人群中共享和适用于微阵列基因分型，全基因组研究现在可以检查更广泛的遗传变异-包括更多样化的变异类型（如插入-删除多态性），变异特定于特定的样本或群体，罕见和低频变异。在此，我们请求继续支持我们在意大利撒丁岛孤立人群中对衰老相关特征的遗传分析，重点是心血管危险因素。在接下来的几年里，我们将使用下一代测序技术和高通量基因分型来研究罕见遗传变异与关键心血管危险因素之间的关系，这些家庭样本包含在Lanusei山谷中招募的约6,000个个体（和1,500,000对近亲）。作为我们计划实验的一部分，我们将评估与测序样本的选择、测序实验和方案的设计、结果序列数据的分析和管理以及最终将结果变体与相关生物医学特征联系起来的关联分析相关的问题。被研究的个体是衰老纵向研究的一部分，他们的心血管特征和结果已经被确定，包括多种关键特征的测量，如血脂水平和血压。我们之前研究了这个样本，以确定与这些心血管特征相关的常见遗传变异，这些变异也会导致心脏病和肥胖的风险。我们提出的实验计划提供了一个独特的机会来评估罕见变异在这个独特样本中的作用。我们期望这些研究将产生实验策略和分析工具，这些实验策略和分析工具将很容易被许多实验室部署，以研究许多其他个体的基因组，并进一步加深我们对许多不同性状和条件的遗传学和生物学的理解。