Organization and Function of Chromosomal Regions that ar

染色体区域的组织和功能

基本信息

项目摘要

Over the past decade, Human Artificial Chromosomes (HACs) have become important models for understanding chromosome structure and function of human centromeres and more recently were used as gene transfer vectors. A gene deficiency in human cells was successfully complemented using HAC vectors, which demonstrates their potential as therapeutic gene expression vectors. To shed light on structural requirements for formation of HACs, we constructed a library of pericentromeric and centromeric regions of the human chromosome 22. The ability of the cloned human centromeric regions to support kinetochore formation in vivo was assessed by their transfection into human cells. HACs formed efficiently with several constructs containing alphoid DNA arrays with homogeneous A-type monomers which form characteristic high order repeats. The alphoid DNA HAC constructs were mitotically stable in the absence of drug selection. In contrast to the published data, our study indicated that CENP-B binding sites may not be required for de novo kinetochore formation. We continued investigation of conditions that maximize the efficiency and selectivity of gene capture by TAR technology in order to make the procedure available to the rest of the scientific community. Specifically, we determined that up to 20% DNA divergence does not prevent efficient gene isolation. Such a tolerance to DNA divergence extended application of TAR cloning to isolation of chromosomal duplications and gene homologs. TAR cloning strategy has been also used for isolation of genomic copies of two tumor suppressor genes, PTEN and a new prostate cancer gene mapped on chromosome Xq27 that was also cloned from patient cells. During the past year, we continued to work on completion of the human chromosome 19 sequence and verification of its contig assemble. Using TAR cloning, four "unclonable" gaps were isolated and sequenced. Thus, our results helped to develop the first contiguous nucleotide sequence of human chromosome.
在过去的十年中,人类人工染色体(HACs)已成为了解人类着丝粒染色体结构和功能的重要模型,最近被用作基因转移载体。使用HAC载体成功地补充了人类细胞中的基因缺陷,这证明了它们作为治疗性基因表达载体的潜力。为了阐明形成HAC的结构要求,我们构建了人类22号染色体的近着丝粒和着丝粒区域的文库。通过将克隆的人着丝粒区域转染到人细胞中来评估其在体内支持动粒形成的能力。用含有α DNA阵列的几种构建体有效地形成了HAC,所述α DNA阵列具有形成特征性高阶重复的同质A型单体。在没有药物选择的情况下,α DNA HAC构建体在有丝分裂上是稳定的。与已发表的数据相反,我们的研究表明,从头动粒形成可能不需要CENP-B结合位点。我们继续研究TAR技术最大限度地提高基因捕获效率和选择性的条件,以便使该程序可用于科学界的其他人。具体地说,我们确定高达20%的DNA分歧不会阻止有效的基因分离。这种对DNA趋异的耐受性将TAR克隆的应用扩展到染色体重复和基因同源物的分离。TAR克隆策略也已用于分离两个肿瘤抑制基因的基因组拷贝,PTEN和定位在染色体Xq 27上的新的前列腺癌基因,其也从患者细胞中克隆。在过去的一年里,我们继续致力于完成人类19号染色体序列的测序和验证其重叠群组装。使用TAR克隆,分离并测序了四个“不可克隆的”缺口。因此,我们的研究结果有助于开发第一个人类染色体的连续核苷酸序列。

项目成果

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VLADIMIR LARIONOV其他文献

VLADIMIR LARIONOV的其他文献

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{{ truncateString('VLADIMIR LARIONOV', 18)}}的其他基金

Human Artificial Chromosomes for Cancer Research and Functional Genomics
用于癌症研究和功能基因组学的人类人工染色体
  • 批准号:
    8937731
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
Human Artificial Chromosomes for Cancer Research and Functional Genomics
用于癌症研究和功能基因组学的人类人工染色体
  • 批准号:
    9556281
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
FUNCTION OF CHROMOSOMAL REGIONS FOR GENOME STABILITY
染色体区域对基因组稳定性的作用
  • 批准号:
    6423821
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
Comparative Analysis of Cancer-Associated Genes and Deve
癌症相关基因的比较分析及开发
  • 批准号:
    7291785
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
Study of hereditary prostate cancer and human artificial chromosomes
遗传性前列腺癌与人类人工染色体的研究
  • 批准号:
    7965305
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
Human Artificial Chromosomes for Cancer Research and Functional Genomics
用于癌症研究和功能基因组学的人类人工染色体
  • 批准号:
    10262084
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
Study of hereditary prostate cancer and human artificial chromosomes
遗传性前列腺癌与人类人工染色体的研究
  • 批准号:
    8349000
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
Study of hereditary prostate cancer and human artificial chromosomes
遗传性前列腺癌与人类人工染色体的研究
  • 批准号:
    8763097
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
Human Artificial Chromosomes for Cancer Research and Functional Genomics
用于癌症研究和功能基因组学的人类人工染色体
  • 批准号:
    10702349
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
Study of hereditary prostate cancer and human artificial chromosomes
遗传性前列腺癌与人类人工染色体的研究
  • 批准号:
    8175316
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:

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职业:表征植物中雌雄异株的重复进化,以设计人工染色体
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通过真菌人工染色体的发育,快速剖析嗜极真菌共培养中产生的抗 MRSA 抗生素的生物合成
  • 批准号:
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Rapid dissection of the biosynthesis of antiMRSA antibiotics produced in co-culture by extremophilic fungi through the development of Fungal Artificial Chromosomes
通过真菌人工染色体的发育,快速剖析嗜极真菌共培养中产生的抗 MRSA 抗生素的生物合成
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21ENGBIO 工程人类人工染色体(HAC)来编码基因组复杂性
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人工染色体的孟德尔遗传
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人工染色体的孟德尔遗传
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利用具有全着丝粒着丝粒的家蚕染色体构建人工染色体
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