Repetitive DNA structure of the human genome

人类基因组的重复DNA结构

• 批准号: 7227510
• 负责人: PETER E WARBURTON
• 金额: $ 30.84万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7227510
• 关键词: 13q; 18p; 21q; Accounting; Affect; Age; Algorithms; Arabidopsis; Base Pairing; Bioinformatics; Biological; Biology; Cataloging; Catalogs; Chromosome Structures; Chromosomes; Chromosomes, Human, Pair 13; Chromosomes, Human, Pair 9; Chromosomes, Human, X; Chromosomes, Human, Y; Class; Code; Computer Analysis; Computer software; Computers; Cruciform DNA; Custom; DNA; DNA Sequence; DNA Sequence Rearrangement; DNA Structure; DNA Transposable Elements; DNA Transposons; DNA biosynthesis; Depth; Disease; Doctor of Philosophy; Elements; Event; Evolution; Extinction (Psychology); Family; Gametogenesis; Gene Conversion; Generations; Genes; Genetic Crossing Over; Genome; Genomics; Germ Cells; Health; Human; Human Chromosomes; Human Genome; Human Genome Project; Left; Length; Location; Meiosis; Meiotic Recombination; Methodology; Methods; Molecular; Molecular Analysis; Molecular Evolution; Mus; Mutation; Natural History; Numbers; Open Reading Frames; Pattern; Population; Positioning Attribute; Primates; Process; Proteins; Pseudogenes; Purpose; Range; Rate; Recording of previous events; Relative (related person); Research Personnel; Retrotransposon; Role; Satellite DNA; Scientist; Selfish DNA; Sex Chromosomes; Shapes; Stretching; Structure; Surveys; Tandem Repeat Sequences; Testis; Time; Today; Upper arm; Variant; X Chromosome; base; density; genome sequencing; genome-wide analysis; heuristics; human DNA sequencing; indexing; insight; male; neglect; novel; programs; size; stem; tool

DESCRIPTION (provided by applicant): The repetitive DNA structure of the human genome The recent completion of the human genome project gives today's scientists the privileged opportunity to provide, for the first and only time, a detailed comprehensive description of the structure of the human DNA sequence. Large parts of our genome remain relatively understudied, especially the repetitive DNA fractions, which account for greater than 45% of our total DNA sequence. Many important genomic turnover mechanisms contribute to the large accumulation of repetitive DNA in our genome, including genomic duplication, transposition, unequal crossing over, and gene conversion, which have a huge impact on the structure of our genome over the course of evolution. Therefore, we propose to undertake the first genome- wide survey and analysis of three distinct aspects of human repetitive DNA, by developing novel computer algorithms, genome analysis tools, and rigourous experimental approaches. 1) We propose to identify and characterize the complete catalogue of human inverted DNA repeats, which have been associated with many important genome functions such as DNA replication, meiotic crossover, and gene conversion. Our results have shown that the human X chromosome contains a preponderance of large highly homologous inverted repeats that contain testes genes. 2) We propose to investigate novel classes of tandemly repeated "satellite" DNA that contain human transposons. These are organized in multiple large arrays primarily in the pericentromeric regions of chromosomes, where rapid chromosome evolution takes place. We have identified and characterized a large family of tandem repeats composed almost entirely of rearranged MaLR LTR transposons, found on 8 different human chromosomes in arrays as large as 70kb. 3) We propose to perform a genome-wide analysis of human transposable elements (TE's) by analyzing the large number of nested transposon clusters where newer TE's have transposed into older TE's. We have developed unique methodology and computer algorithms that can locate and index all such transposon clusters in the human genome, and can derive a relative chronological order of human TEs over the course of evolution. This represents a completely novel method of studying molecular evolution that is not dependent on the assumption of a constant mutation rate (molecular clock). The studies proposed in this application will facilitate both computational and biological approaches to genomics and provide a unique analysis of a large and relatively neglected portion of our DNA sequence.

描述(申请人提供)：人类基因组的重复DNA结构最近人类基因组计划的完成使今天的科学家有机会第一次也是唯一一次提供对人类DNA序列结构的详细而全面的描述。我们基因组的很大一部分仍然相对较少被研究，特别是占我们总DNA序列45%以上的重复DNA片段。许多重要的基因组周转机制导致了重复DNA在我们基因组中的大量积累，包括基因组复制、转座、不等交换和基因转换，这些机制在进化过程中对我们的基因组结构产生了巨大的影响。因此，我们建议通过开发新的计算机算法、基因组分析工具和严格的实验方法，对人类重复DNA的三个不同方面进行首次全基因组调查和分析。1)我们建议鉴定和鉴定人类反向DNA重复序列的完整目录，这些重复序列与许多重要的基因组功能相关，如DNA复制、减数分裂交叉和基因转换。我们的结果表明，人类X染色体包含大量含有睾丸基因的高度同源的大的反向重复序列。2)我们建议研究含有人类转座子的新型重复“卫星”DNA。它们被组织成多个大的阵列，主要在染色体的着丝粒周围区域，那里发生了快速的染色体进化。我们已经鉴定和鉴定了一个几乎完全由重排的MaLR LTR转座子组成的串联重复序列大家族，这些转座子发现于8条不同的人类染色体上，大小为70kb。3)我们建议对人类转座元件(TE‘s)进行全基因组分析，通过分析大量嵌套的转座子簇，其中较新的TE已经转座到较老的TE’s。我们开发了独特的方法和计算机算法，可以定位和索引人类基因组中所有这样的转座子簇，并可以推导出人类TES在进化过程中的相对时间顺序。这代表了一种研究分子进化的全新方法，它不依赖于恒定突变率(分子时钟)的假设。这项申请中提出的研究将促进基因组学的计算和生物学方法，并提供对我们DNA序列中较大且相对被忽视的部分的独特分析。