Exhaustive Analysis of Microsatellite Loci in the 1000 Genomes Project

千个基因组计划中微卫星位点的详尽分析

• 批准号: 7882989
• 负责人: HAROLD R GARNER
• 金额: $ 26.4万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-26 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7882989
• 关键词: Area; Biological Markers; Characteristics; DNA; DNA Sequence; Data; Disease; Elements; Exhibits; Family; Forensic Medicine; Genes; Genetic Polymorphism; Genome; Genomics; Goals; Human; Human Genome; Individual; Instruction; Internet; Laboratories; Length; Measurement; Measures; Metadata; Methods; Microsatellite Repeats; Modeling; Ontology; Paternity testing; Principal Investigator; Process; Reagent; Repetitive Sequence; Research; Resources; Role; Single Nucleotide Polymorphism; Techniques; Variant; cohort; genome sequencing; genome-wide; pressure; trend; user-friendly

DESCRIPTION (provided by applicant): The study of repetitive DNA, microsatellites, a class of genomic variation which exhibits a 10,000 fold higher mutability than single nucleotide polymorphisms has been hampered by the lack of data at microsatellite- containing loci. That is, until now, with the emergence of data from the 1000 Genomes Project. We hypothesize that these hypervariable loci, once analyzed in depth will yield a new appreciation for their value and role in the genome as new biomarkers and functional elements. Baseline measurements of the variability at these loci in the substantial 1000 Genomes Project cohort will provide important information required to exploit these loci, both computationally and in the laboratory. The primary goal of the proposed research is to complete an exhaustive analysis and interpretation of the ~700,000 microsatellite loci using the -2,500 sets of genome sequence becoming available from the 1000 Genomes Project to measure their size, purity and motif dependent distributions and then overlay those data with metadata (gene ontologies, conservation and more) to create a resource where we an others can explore the significant, yet underappreciated role of microsatellite polymorphism in human variation and disease. We have demonstrated the techniques required and impactful preliminary results confirm feasibility and value and potential. Specific aims 1) align all 1000 Genomes Project sequence data to the microsatellite containing loci to measure the allelic distribution, polymorphism rate, characteristics, quality of the sequence in these repetitive regions; inspect and characterize groups of motif lengths and families (AAT,AAAT,AATT, etc.) to look for evidence for selection pressure, bias and genome wide trends; 2) compare the distributions with models for estimating polymorphism propensity as a function of specific sequence motifs, motif size, copies and purity (are there any SNPs), thus identifying any general replication or error correction mechanism bias, which we suspect; 3) annotate each locus with ontology, conservation and other positional data to identify any process, functional or disease propensity correlations; and 4) create a web resource to distribute our findings and other reagents derived from this study so others can investigate microsatellite sequence variability at individual loci or across the genome. RELEVANCE (See instructions): The human genome contains over 500,000 areas with repeated DNA sequence (e.g. CACACACACA) called microsatellites. They are extremely variable, cause numerous diseases, are used in forensics/ paternity testing and may alter many of our characteristics, but they are understudied and under- appreciated. The 1000 Genome Project data enables their thorough analysis en masse by our methods.

描述（由申请人提供）：重复DNA、微卫星、一类表现出比单核苷酸多态性高10，000倍的突变性的基因组变异的研究由于缺乏含微卫星基因座的数据而受到阻碍.也就是说，直到现在，随着1000个基因组计划数据的出现。我们假设，这些高变基因座，一旦深入分析，将产生一个新的升值的价值和作用，在基因组中作为新的生物标志物和功能元件。基线测量的变异性在这些基因座在大量的1000个基因组计划的队列将提供重要的信息，利用这些基因座，无论是在计算和实验室。所提出的研究的主要目标是使用从1000个基因组计划获得的~ 2,500组基因组序列来完成对~ 700，000个微卫星位点的详尽分析和解释，以测量它们的大小、纯度和基序依赖性分布，然后将这些数据与元数据叠加。（基因本体论，保护和更多）创造一个资源，我们和其他人可以探索显着的，但未被充分认识的作用，微卫星多态性在人类的变化和疾病。我们已经展示了所需的技术，有效的初步结果证实了可行性、价值和潜力。具体目标1）将所有1000个基因组计划序列数据与含有微卫星的位点进行比对，以测量这些重复区域中序列的等位基因分布、多态性率、特征、质量;检查和表征基序长度和家族（AAT、AAAT、AATT等）的组。寻找选择压力、偏倚和全基因组趋势的证据; 2）将分布与用于估计作为特定序列基序、基序大小、拷贝和纯度的函数的多态性倾向的模型进行比较（是否存在任何SNP），从而确定我们怀疑的任何一般复制或纠错机制偏倚; 3）用本体、守恒和其他位置数据注释每个位点以识别任何过程、功能或疾病倾向相关性;和4）创建网络资源以分发我们的发现和来自本研究的其他试剂，以便其他人可以研究单个基因座或整个基因组的微卫星序列变异性。相关性（参见说明）：人类基因组包含超过50万个具有重复DNA序列（例如CACACACA）的区域，称为微卫星。它们是极其可变的，导致许多疾病，用于法医/亲子鉴定，并可能改变我们的许多特征，但它们是研究不足和低估。千人基因组计划的数据使他们能够通过我们的方法进行全面的分析。