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    Methods for Genotyping Polymorphisms
    1.
    发明申请
    Methods for Genotyping Polymorphisms 审中-公开
    多态性基因分型方法

    公开(公告)号：US20090131268A1

    公开(公告)日：2009-05-21

    申请号：US12211103

    申请日：2008-09-15

    申请人： Paul Hardenbol ,  Jonathan E. Forman ,  George Karlin-Neumann ,  Xin Miao

    发明人： Paul Hardenbol ,  Jonathan E. Forman ,  George Karlin-Neumann ,  Xin Miao

    IPC分类号： C40B30/04

    CPC分类号： C12Q1/6883 ,  C12Q2600/106 ,  C12Q2600/156 ,  C12Q2600/16

    摘要： The invention provides method for genotyping specific sets of polymorphisms in a single multiplex reaction. The polymorphisms are selected to be of interest in detecting genetic variation that alters individuals' metabolism, distribution, extretion and transport of pharmacological compounds. In preferred aspects the genotyping employs a multiplex hybridization-based assay. In some aspects combinations of methods are employed to allow the combination of polymorphisms to be interrogated. The invention also provides nucleic acid standards for validating the performance of such hybridization-based assays.

    摘要翻译： 本发明提供了在单个多重反应中对特定多态性集进行基因分型的方法。 选择多态性来检测改变个体代谢，分布，排泄和运输药理化合物的遗传变异。 在优选方面，基因分型采用基于多重杂交的测定法。 在某些方面，采用方法的组合来允许询问多态性的组合。 本发明还提供用于验证这种基于杂交的测定的性能的核酸标准。

    System and methods for enhancing signal-to-noise ratios of microarray-based measurements
    2.
    发明申请
    System and methods for enhancing signal-to-noise ratios of microarray-based measurements 审中-公开
    用于增强基于微阵列的测量的信噪比的系统和方法

    公开(公告)号：US20050100939A1

    公开(公告)日：2005-05-12

    申请号：US10943752

    申请日：2004-09-17

    申请人： Eugeni Namsaraev ,  George Karlin-Neumann ,  Malek Faham ,  Maneesh Jain ,  Paul Hardenbol ,  Thomas Willis ,  Zhiyong Wang

    发明人： Eugeni Namsaraev ,  George Karlin-Neumann ,  Malek Faham ,  Maneesh Jain ,  Paul Hardenbol ,  Thomas Willis ,  Zhiyong Wang

    IPC分类号： C12Q1/68 ,  G01N20060101 ,  G01N33/48 ,  G01N33/50 ,  G06F19/00

    CPC分类号： C12Q1/6837 ,  C12Q2563/131

    摘要： The present invention provides systems and methods for large-scale genetic measurements by generating from a sample labeled target sequences whose length, orientation, label, and degree of overlap and complementarity are tailored to corresponding end-attached probes of a solid support so that signal-to-noise ratios of measurement from specifically hybridized labeled target sequences are maximized. Systems for implementing methods of the invention include a set of sample-interacting probes to produce amplicons that either each contain a segment of a target polynucleotide or an oligonucleotide tag that corresponds to a segment of a target polynucleotide, one or more solid phase supports that contain a plurality of end-attached probes, and methods of generating from sample-interacting probe amplicons from which labeled target sequences are tailored for hybridization to the solid phase supports, such as microarrays. In one aspect, labeled target sequences and end-attached probe of the solid phase supports comprise oligonucleotide tags and tag complements, respectively, selected from a minimally cross-hybridizing set.

    摘要翻译： 本发明提供了用于大规模遗传测量的系统和方法，所述系统和方法通过从样品标记的靶序列产生，所述样品标记的靶序列的长度，取向，标记，重叠度和互补度被量化到固体支持物的相应末端附接探针， 来自特异性杂交的标记靶序列的测量的信噪比最大化。 用于实施本发明方法的系统包括一组样品相互作用探针以产生扩增子，每个扩增子各含有靶多核苷酸片段或对应于靶多核苷酸片段的寡核苷酸标签，一个或多个固相载体含有 多个末端连接的探针，以及从样品相互作用的探针扩增子产生的方法，其中标记的靶序列被定制用于与固相支持物例如微阵列杂交。 在一个方面，固相载体的标记的靶序列和末端连接的探针分别包含选自最小交叉杂交组的寡核苷酸标签和标签互补物。

    Simultaneous analysis of multiple genomes
    3.
    发明申请
    Simultaneous analysis of multiple genomes 审中-公开
    同时分析多个基因组

    公开(公告)号：US20060019304A1

    公开(公告)日：2006-01-26

    申请号：US11189486

    申请日：2005-07-25

    申请人： Paul Hardenbol ,  George Karlin-Neumann ,  Thomas Willis ,  Maneesh Jain ,  Nicholas Naclerio

    发明人： Paul Hardenbol ,  George Karlin-Neumann ,  Thomas Willis ,  Maneesh Jain ,  Nicholas Naclerio

    IPC分类号： C12Q1/68 ,  G06F19/00

    CPC分类号： C12Q1/6837 ,  C12Q1/6858 ,  C12Q2537/143 ,  C12Q2525/161 ,  C12Q2533/107

    摘要： The invention provides methods for multiplexing readouts from multiple hybridization-based assays that each comprise one or more hybridization or annealing steps and one or more enzymatic processing steps. In one aspect, the invention permits simultaneously analysis of a plurality of genomes by separately hybridizing a set of probes with the different genomes to form sets of probe-genome complexes in separate reaction mixtures that are combined and enzymatically treated to form amplifiable probes. From such amplifiable probes, labeled probes are produced so that for each different locus of each different genome there is a unique labeled probe, which are then specifically hybridized to their respective complements on a microarray. In another aspect, labeled oligonucleotide tags are produced from amplifiable probes. The invention is useful in applications of multiplexed hybridization-based assays for measuring characteristics of genomic samples taken from many different individuals. By conducting hybridization steps separately on samples different individuals then combining them for enzymatic processing, one takes advantage of natural reaction rate differences between hybridization reactions and enzymatic reactions to enable analysis of products of multiple assays on a single readout platform.

    摘要翻译： 本发明提供了用于从多个基于杂交的测定中复用读出的方法，每个测序包含一个或多个杂交或退火步骤和一个或多个酶处理步骤。 一方面，本发明允许通过将一组探针与不同基因组分开杂交来同时分析多个基因组，以在组合和酶处理以形成可扩增探针的分开的反应混合物中形成探针 - 基因组复合物组。 从这样的可扩增探针中产生标记的探针，使得对于每个不同基因组的每个不同基因座，存在唯一标记的探针，然后在微阵列上与其各自的互补序列特异性杂交。 另一方面，标记的寡核苷酸标签由可扩增的探针产生。 本发明在多基于杂交的测定用于测量从许多不同个体获取的基因组样品的特征的应用中是有用的。 通过分别对样品进行杂交步骤，然后将它们组合用于酶处理，一个利用杂交反应和酶反应之间的天然反应速率差异，以使得能够在单个读出平台上分析多个测定的产物。

    Methods and Kits for Multiplex Hybridization Assays
    4.
    发明申请
    Methods and Kits for Multiplex Hybridization Assays 审中-公开
    多重杂交试验方法和试剂盒

    公开(公告)号：US20080206779A1

    公开(公告)日：2008-08-28

    申请号：US12116064

    申请日：2008-05-06

    申请人： Xin Miao ,  James Ireland ,  Paul Hardenbol ,  Thomas Matthew Daly ,  Dong-Jing Fu ,  Richard D. Hockett

    发明人： Xin Miao ,  James Ireland ,  Paul Hardenbol ,  Thomas Matthew Daly ,  Dong-Jing Fu ,  Richard D. Hockett

    IPC分类号： C12Q1/68

    CPC分类号： C12Q1/6827 ,  C12Q2521/501

    摘要： The invention provides a method for genotyping interfering polymorphic loci in a target polynucleotide, such as a strand of genomic DNA, in a multiplex hybridization-based assay. The invention also provides nucleic acid standards for validating the performance of such hybridization-based assays. In one aspect, the method of the invention is carried out by providing for each interfering polymorphic locus one or more probes so that at least one probe is capable of forming a perfectly match duplex at the locus regardless of the characteristic sequence of an adjacent polymorphism.

    摘要翻译： 本发明提供了一种用于基于多重杂交的测定法在靶多核苷酸（例如基因组DNA链）中基因分型干扰多态性基因座的方法。 本发明还提供用于验证这种基于杂交的测定的性能的核酸标准。 在一个方面，本发明的方法是通过为每个干扰多态性位点提供一个或多个探针来进行的，使得至少一个探针能够在所述位点形成完全匹配的双链体，而与相邻多态性的特征序列无关。

    Method and kits for multiplex hybridization assays
    5.
    发明申请
    Method and kits for multiplex hybridization assays 有权
    多重杂交测定法和试剂盒

    公开(公告)号：US20060281098A1

    公开(公告)日：2006-12-14

    申请号：US11152460

    申请日：2005-06-14

    申请人： Xin Miao ,  James Ireland ,  Paul Hardenbol ,  Thomas Daly ,  Dong-Jing Fu ,  Richard Hockett

    发明人： Xin Miao ,  James Ireland ,  Paul Hardenbol ,  Thomas Daly ,  Dong-Jing Fu ,  Richard Hockett

    IPC分类号： C12Q1/68

    CPC分类号： C12Q1/6827 ,  C12Q2521/501

    摘要： The invention provides a method for genotyping interfering polymorphic loci in a target polynucleotide, such as a strand of genomic DNA, in a multiplex hybridization-based assay. The invention also provides nucleic acid standards for validating the performance of such hybridization-based assays. In one aspect, the method of the invention is carried out by providing for each interfering polymorphic locus one or more probes so that at least one probe is capable of forming a perfectly match duplex at the locus regardless of the characteristic sequence of an adjacent polymorphism.

    摘要翻译： 本发明提供了一种用于基于多重杂交的测定法在靶多核苷酸（例如基因组DNA链）中基因分型干扰多态性基因座的方法。 本发明还提供用于验证这种基于杂交的测定的性能的核酸标准。 在一个方面，本发明的方法是通过为每个干扰多态性位点提供一个或多个探针来进行的，使得至少一个探针能够在所述位点形成完全匹配的双链体，而与相邻多态性的特征序列无关。

    Method and kits for multiplex hybridization assays
    6.
    发明授权
    Method and kits for multiplex hybridization assays 有权
    多重杂交测定法和试剂盒

    公开(公告)号：US07368242B2

    公开(公告)日：2008-05-06

    申请号：US11152460

    申请日：2005-06-14

    申请人： Xin Miao ,  James Ireland ,  Paul Hardenbol ,  Thomas Matthew Daly ,  Dong-Jing Fu ,  Richard D. Hockett

    发明人： Xin Miao ,  James Ireland ,  Paul Hardenbol ,  Thomas Matthew Daly ,  Dong-Jing Fu ,  Richard D. Hockett

    IPC分类号： C12Q1/68 ,  C07H21/02 ,  C07H21/04

    CPC分类号： C12Q1/6827 ,  C12Q2521/501

    摘要： The invention provides a method for genotyping interfering polymorphic loci in a target polynucleotide, such as a strand of genomic DNA, in a multiplex hybridization-based assay. The invention also provides nucleic acid standards for validating the performance of such hybridization-based assays. In one aspect, the method of the invention is carried out by providing for each interfering polymorphic locus one or more probes so that at least one probe is capable of forming a perfectly match duplex at the locus regardless of the characteristic sequence of an adjacent polymorphism.

    摘要翻译： 本发明提供了一种用于基于多重杂交的测定法在靶多核苷酸（例如基因组DNA链）中基因分型干扰多态性基因座的方法。 本发明还提供用于验证这种基于杂交的测定的性能的核酸标准。 在一个方面，本发明的方法是通过为每个干扰多态性位点提供一个或多个探针来进行的，使得至少一个探针能够在所述位点形成完全匹配的双链体，而与相邻多态性的特征序列无关。

    Multiplex polynucleotide synthesis
    7.
    发明申请
    Multiplex polynucleotide synthesis 审中-公开
    多重多核苷酸合成

    公开(公告)号：US20060234264A1

    公开(公告)日：2006-10-19

    申请号：US11375818

    申请日：2006-03-14

    申请人： Paul Hardenbol

    发明人： Paul Hardenbol

    IPC分类号： C12Q1/68 ,  C12P19/34

    CPC分类号： C12P19/34

    摘要： The invention provides a method of synthesizing complex mixtures of long polynucleotides by separately synthesizing and assembling shorter component oligonucleotides. In one aspect, pairs of oligonucleotides that form components of such polynucleotides are synthesized on one or more microarrays, or other large-scale parallel solid phase synthesis platforms, after which they are released. Members of each pair contain unique complementary barcode sequences that are used match-up pairs in a hybridization reaction to form duplexes. Such duplexes are then extended with a DNA polymerase and the resulting extension product is amplified to form an amplicon. The amplicon may be either used directly as the desired polynucleotide, or it may undergo further processing, such as capture on solid phase supports and/or additional enzymatic or chemical processing, to produce a desired polynucleotide product, such as a circularizing probe for multiplex analysis of genomic DNA, or the like.

    摘要翻译： 本发明提供了通过单独合成和组装较短组分寡核苷酸来合成长多核苷酸的复合混合物的方法。 在一个方面，形成这种多核苷酸的组分的寡核苷酸对在一个或多个微阵列或其它大规模平行固相合成平台上合成，之后它们被释放。 每对的成员包含独特的互补条形码序列，其在杂交反应中使用匹配对形成双链体。 然后用DNA聚合酶扩增此类双链体，并将所得延伸产物扩增以形成扩增子。 扩增子可以直接用作所需的多核苷酸，或者可以进行进一步处理，例如在固相载体上捕获和/或另外的酶或化学处理，以产生所需的多核苷酸产物，例如用于多重分析的环化探针 的基因组DNA等。