The repetitive DNA structure of the human genome

人类基因组的重复DNA结构

基本信息

批准号：
7614255
负责人：
PETER E WARBURTON
金额：
$ 30.89万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
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/7614255
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 Code Computer Analysis Computer software Computers Cruciform DNA Custom DNA DNA Sequence DNA Sequence Rearrangement DNA Structure DNA Transposable Elements DNA Transposons DNA biosynthesis 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 Open Reading Frames Pattern Population Positioning Attribute Primates Process Proteins Pseudogenes 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 Upper arm Variant X Chromosome base density genome sequencing genome wide association study genome-wide genome-wide analysis heuristics human DNA sequencing indexing insight male neglect novel programs stem tool

项目摘要

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（由申请人提供）：人类基因组的重复DNA结构人类基因组项目的最新完成为当今的科学家提供了特权的机会，可以在第一个也是唯一的时间内提供对人DNA序列结构的详细综合描述。我们的大部分基因组仍然相对研究，尤其是重复的DNA级分，占我们总DNA序列的45％以上。许多重要的基因组周转机制有助于我们的基因组中重复的DNA大量积累，包括基因组重复，转座，不平等的交叉和基因转化，这在进化过程中对我们的基因组的结构产生了巨大影响。因此，我们建议通过开发新颖的计算机算法，基因组分析工具和严格的实验方法对人类重复性DNA的三个不同方面进行首次基因组进行调查和分析。 1）我们建议识别和表征人类倒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函数有关，例如DNA复制，减数分裂交叉和基因转换。我们的结果表明，人X染色体含有大型高度同源的倒置重复序列，其中包含睾丸基因。 2）我们建议研究包含人类转座子的新型串联重复的“卫星” DNA。这些主要在多个大型阵列中组织，主要是在染色体的周围层粒区域中，在那里发生了快速的染色体进化。我们已经确定并表征了一个大家族的串联重复，几乎完全由重排的MALR LTR转座子组成，在阵列中的8种不同的人类染色体上发现，在70kb的阵列中。 3）我们建议通过分析大量嵌套的转座子簇对人类转座元素（TE）进行全基因组分析，这些嵌套的转座簇已转移到较旧的TE中。我们已经开发了独特的方法论和计算机算法，这些方法和计算机算法可以在人类基因组中定位和索引所有此类转座子簇，并可以在进化过程中得出人类TES的相对时间顺序。这代表了研究分子进化的一种完全新颖的方法，该方法不取决于恒定突变率（分子钟）的假设。本应用中提出的研究将促进基因组学的计算和生物学方法，并对我们的DNA序列的大部分且相对被忽视的部分提供独特的分析。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Evolutionary history of mammalian transposons determined by genome-wide defragmentation.

DOI：
10.1371/journal.pcbi.0030137
发表时间：
2007-07
期刊：
PLoS computational biology
影响因子：
4.3
作者：
Giordano J;Ge Y;Gelfand Y;Abrusán G;Benson G;Warburton PE
通讯作者：
Warburton PE

The distribution of inverted repeat sequences in the Saccharomyces cerevisiae genome.

DOI：
10.1007/s00294-010-0302-6
发表时间：
2010-08
期刊：
CURRENT GENETICS
影响因子：
2.5
作者：
Strawbridge, Eva M.;Benson, Gary;Gelfand, Yevgeniy;Benham, Craig J.
通讯作者：
Benham, Craig J.

Analysis of the largest tandemly repeated DNA families in the human genome.

DOI：
10.1186/1471-2164-9-533
发表时间：
2008-11-07
期刊：
BMC GENOMICS
影响因子：
4.4
作者：
Warburton, Peter E.;Hasson, Dan;Guillem, Flavia;Lescale, Chloe;Jin, Xiaoping;Abrusan, Gyorgy
通讯作者：
Abrusan, Gyorgy