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    RIBONUCLEOTIDE TAG NUCLEIC ACID DETECTION
    1.
    发明申请
    RIBONUCLEOTIDE TAG NUCLEIC ACID DETECTION 审中-公开

    公开(公告)号：US20090263813A1

    公开(公告)日：2009-10-22

    申请号：US12421188

    申请日：2009-04-09

    申请人： DAVID H GELFAND ,  Ivo Glynne Gut ,  Keith A. Bauer ,  Florence Mauger

    发明人： DAVID H GELFAND ,  Ivo Glynne Gut ,  Keith A. Bauer ,  Florence Mauger

    IPC分类号： C12Q1/68

    CPC分类号： C12Q1/6858 ,  C12Q1/686

    摘要： The present application provides polynucleotides comprising 5′-tails with sequence segments useful for the detection of target nucleic acid sequences, and methods for their use in detecting target nucleic acids. The polynucleotides are used to amplify a subsequence of a target nucleic acid in the presence of one or more ribonucleotides. The ribonucleotides are incorporated into amplification products at regular intervals complementary to the 5′-tail sequence segments. Cleavage of amplification products at the bond immediately 3′ to incorporated ribonucleotides produces detectably distinct fragments indicative of the presence or absence of a target nucleic acid.

    摘要翻译： 本申请提供了包含具有用于检测靶核酸序列的序列区段的5'-尾的多核苷酸，以及它们用于检测靶核酸的方法。 多核苷酸用于在一个或多个核糖核苷酸存在下扩增靶核酸的亚序列。 核糖核苷酸以与5'-尾序列片段互补的规则间隔掺入扩增产物中。 立即将3'端的扩增产物切割成掺入的核糖核苷酸产生指示靶核酸存在或不存在的可检测的不同片段。

    METHOD FOR TESTING A SUBJECT THOUGHT TO HAVE OR TO BE PREDISPOSED TO ASTHMA
    3.
    发明申请
    METHOD FOR TESTING A SUBJECT THOUGHT TO HAVE OR TO BE PREDISPOSED TO ASTHMA 审中-公开
    测试一个或多或待预测到ASTHMA的主体的方法

    公开(公告)号：US20110046202A1

    公开(公告)日：2011-02-24

    申请号：US12665602

    申请日：2008-06-19

    申请人： Miriam Fleur Moffat ,  William Osmond Charles Cookson ,  Ivo Glynne Gut ,  Gregory Mark Lathrop ,  Michael Kabesch ,  Martin Farral ,  Goncalo Rocha Abecasis ,  Liming Liang

    发明人： Miriam Fleur Moffat ,  William Osmond Charles Cookson ,  Ivo Glynne Gut ,  Gregory Mark Lathrop ,  Michael Kabesch ,  Martin Farral ,  Goncalo Rocha Abecasis ,  Liming Liang

    IPC分类号： A61K31/713 ,  C12Q1/68 ,  C40B30/04 ,  A61P11/06 ,  A61P37/08

    CPC分类号： G01N33/6893 ,  G01N2500/10 ,  G01N2800/122 ,  G01N2800/24

    摘要： The present invention concerns a method of testing a subject thought to have or be predisposed to having asthma, allergy, atopic disease or atopic sensitization, which comprises the step of analyzing a biological sample from said subject for (i) detecting the presence of a mutation associated with the over-expression of the ORMDL3 gene, and/or (ii) analyzing the expression of the ORMDL3 gene; a use, for treating and/or preventing asthma, allergy, atopic disease or atopic sensitization in a subject, of a compound which specifically inhibits the expression of the ORMDL3 gene; and an in vitro method of selecting a compound, which can be useful for treating asthma, allergy, atopic disease or atopic sensitization, characterized in that said method comprises the steps of: (a) obtaining a cell expressing the ORMDL3 gene, (b) contacting said cell with at least one compound, (c) comparing the expression of the ORMDL3 gene in the cell between the steps a) and b), and (d) selecting the compound, which induces a lower level of expression of the ORMDL3 gene in the cell contacted to that compound.

    摘要翻译： 本发明涉及一种测试被认为具有哮喘，过敏，特应性疾病或特应性敏化的受试者的方法，其包括分析来自所述受试者的生物样品的步骤：（i）检测突变的存在 与ORMDL3基因的过表达相关，和/或（ii）分析ORMDL3基因的表达; 用于治疗和/或预防受试者中特异性抑制ORMDL3基因表达的化合物的哮喘，过敏，特应性疾病或特应性敏化的用途; 以及选择可用于治疗哮喘，过敏，特应性疾病或特应性敏化的化合物的体外方法，其特征在于所述方法包括以下步骤：（a）获得表达ORMDL3基因的细胞，（b） 使所述细胞与至少一种化合物接触，（c）比较步骤a）和b）之间的细胞中ORMDL3基因的表达，和（d）选择诱导ORMDL3基因表达水平较低的化合物 在与该化合物接触的细胞中。

    METHOD OF IMAGING BY MASS SPECTROMETRY AND NEW MASS TAG ASSOCIATED TRITYL DERIVATIVES
    4.
    发明申请
    METHOD OF IMAGING BY MASS SPECTROMETRY AND NEW MASS TAG ASSOCIATED TRITYL DERIVATIVES 审中-公开
    通过大量光谱法和新的质量标签相关三氯乙烯衍生物成像方法

    公开(公告)号：US20110223613A1

    公开(公告)日：2011-09-15

    申请号：US13062160

    申请日：2009-09-04

    申请人： Ivo Glynne Gut

    发明人： Ivo Glynne Gut

    IPC分类号： G01N21/75 ,  C07D207/46

    CPC分类号： C07C235/32 ,  C09B11/04 ,  G01N33/532 ,  G01N33/6848 ,  G01N2458/15

    摘要： The present invention concerns a method of analyzing at least one specific molecule in a sample using a compound of formula (I″) wherein Z binds specifically to said at least one specific molecule, Y is independently a cleavable single bond, linker atom or group, and R is independently a substituent such as H, C1-20 hydrocarbonyl {e.g. C1-20 alkyl, C1-20 aryl) or substituted C1-20 hydrocarbonyl. Preferably, the method of the invention is carried out with mass spectroscopy in a spectrometer.

    摘要翻译： 本发明涉及使用式（I“）化合物分析样品中的至少一种特定分子的方法，其中Z与所述至少一种特定分子特异性结合，Y独立地是可切割单键，连接原子或基团， 并且R独立地是取代基，例如H，C 1-20烃基（例如， C 1-20烷基，C 1-20芳基）或取代的C 1-20烃基。 优选地，本发明的方法在光谱仪中用质谱法进行。

    METHOD FOR HLA TYPING
    6.
    发明申请
    METHOD FOR HLA TYPING 有权
    HLA型方法

    公开(公告)号：US20120157347A1

    公开(公告)日：2012-06-21

    申请号：US12881867

    申请日：2010-09-14

    申请人： Ivo Glynne Gut ,  Ramon Kucharzak

    发明人： Ivo Glynne Gut ,  Ramon Kucharzak

    IPC分类号： C40B40/06

    CPC分类号： C12Q1/6881 ,  C12Q1/6827 ,  C12Q1/6872 ,  C12Q2600/156 ,  C12Q2600/172 ,  C12Q2565/627 ,  C12Q2537/143 ,  C12Q2535/125

    摘要： A method for the identification of DNA sequence elements in complex and highly variable sequences is described. The method considist of identifying a short sequence element of several DNA bases (2-6 bases) at a given position in the genome simultaneously on all parental alleles. The method allows differentiating mini-haplotypes on different alleles in one analysis. The method consists of carrying out an enzymatic primer extension reaction with a combination of extension primers (pool of primers) and analyzing the products by mass spectrometry. The pool of primers is assembled in such a way that the primer extension product allows unambiguous identification of both the primer of the pool that was extended and the base that was added. The method of great utility for DNA sequences harbouring many SNP's close to each other with many possible haplotypes. Such sequences are known in the Major Histocompatibility Complex (MHC). This method is particularly well suited for DNA-based HLA typing and in combination with a suitable selection of sites tested, it is superior in ease of operation to conventional HLA typing methods. We have identified sets of these assays for HLA-A, HLA-B, and HLA-DRB 1 that allow unambiguous four-digit HLA of each of these genes with between 11 and 28 queried markers.

    摘要翻译： 描述了用于鉴定复杂和高度可变序列中的DNA序列元件的方法。 该方法考虑在所有亲本等位基因中同时鉴定基因组中给定位置上几个DNA碱基（2-6个碱基）的短序列元件。 该方法允许在一个分析中区分不同等位基因上的微型单倍型。 该方法包括用扩增引物（引物库）进行酶引发延伸反应，并通过质谱分析产物。 以这样的方式组装引物池，使得引物延伸产物允许明确鉴定扩展的池的引物和所添加的碱基。 对于具有许多可能的单倍型的许多SNP彼此接近的DNA序列具有很大效用的方法。 这些序列在主要组织相容性复合体（MHC）中是已知的。 该方法特别适用于基于DNA的HLA分型，并结合适当选择的测试位点，其操作方便性优于常规HLA分型方法。 我们已经确定了HLA-A，HLA-B和HLA-DRB 1的这些测定集，这些测定允许这些基因中的每一个具有11到28个查询标记的明确的四位数HLA。

    Two-step method of DNA amplification for MALDI-TOF measurement
    7.
    发明授权
    Two-step method of DNA amplification for MALDI-TOF measurement 失效
    MALDI-TOF测定的DNA扩增两步法

    公开(公告)号：US06303298B1

    公开(公告)日：2001-10-16

    申请号：US09036279

    申请日：1998-03-06

    申请人： Ivo Glynne Gut ,  Jochen Franzen

    发明人： Ivo Glynne Gut ,  Jochen Franzen

    IPC分类号： C12Q168

    CPC分类号： C12Q1/686 ,  Y10T436/24 ,  C12Q2563/167 ,  C12Q2563/143 ,  C12Q2565/627 ,  C12Q2565/518

    摘要： The invention referres to a method for the preparation and selective replication of deoxyribonucleic acid (DNA) from biomaterial using PCR (polymerase chain reaction) for the analysis in time-of-flight mass spectrometers (TOF) with matrix-assisted laser desorption and ionization (MALDI) for determining specific genetic features in biomaterial. The invention consists, in a first step, of replicating the selected DNA segments by the PCR method in the usual unmodified fashion, and in a further enzymatic replication process, to replicate the DNA segments using modified substrates (the nucleic acids used for PCR) and specially prepared primers to such DNA analogs as are especially suitable for ionization by MALDI. Preparation of the primers particularly consists of introducing a charged group, which improves the ionization, and modification of the substrates is used to neutralize the negative charge on the phosphoric acid group of the DNA backbone. It is especially practical to immobilize the DNA on a surface for the fmal enzymatic reduplication process, for example on a prepared MALDI layer located on magnetic beads. In the final reduplication process, extremely little reagent is used, thus it is also possible in terms of low cost to use isotope-enriched material here in order to increase the mass resolving power.

    摘要翻译： 本发明涉及一种使用PCR（聚合酶链式反应）从生物材料制备和选择性复制脱氧核糖核酸（DNA）的方法，用于基质辅助激光解吸和电离（TOF）的飞行时间质谱仪（TOF） MALDI），用于确定生物材料中的特定遗传特征。 本发明包括在第一步中通过PCR方法以通常的未修饰方式复制选定的DNA片段，并在另外的酶促复制过程中，使用修饰底物（用于PCR的核酸）复制DNA片段;以及 特别制备的引物，特别适用于通过MALDI电离的DNA类似物。 引物的制备特别包括引入提高电离的带电基团，并且修饰底物用于中和DNA骨架的磷酸基上的负电荷。 将DNA固定在用于热的酶重复制备过程的表面上是特别实用的，例如在位于磁珠上的制备的MALDI层上。 在最终重复制造过程中，使用极少的试剂，因此在这里使用同位素富集材料的成本低也是可能的，以便提高质量分辨能力。

    Mutation analysis using mass spectrometry
    9.
    发明授权
    Mutation analysis using mass spectrometry 失效
    使用质谱进行突变分析

    公开(公告)号：US06503710B2

    公开(公告)日：2003-01-07

    申请号：US09321005

    申请日：1999-05-27

    申请人： Ivo Glynne Gut ,  Kurt Berlin ,  Doris Lechner ,  Hans Lehrach

    发明人： Ivo Glynne Gut ,  Kurt Berlin ,  Doris Lechner ,  Hans Lehrach

    IPC分类号： C07H2104

    CPC分类号： C12Q1/6827 ,  Y10T436/24 ,  Y10T436/25125 ,  C12Q2563/167

    摘要： The invention presents a method for examining genetic material (deoxyribonucleic acid, DNA) to detect the presence of pre-known mutations, especially single nucleotide polymorphisms (SNP), using mass spectrometry with ionization by matrix-assisted laser desorption (MALDI). The invention uses nucleoside triphosphates with modified sites for the method of primer extension in a duplicating, enzymatic reaction and at least partially removal of primers from the extension product, in combination with product neutralization by chemical treatment of the modified sites, so that the resulting DNA products can be, by using special matrix materials, preferredly ionized in an adduct-free form over other constituents in the reaction solution without any further cleaning. The method is particularly suitable for simultaneous identification of several mutations by multiplexing.

    摘要翻译： 本发明提出了一种使用通过基质辅助激光解吸（MALDI）电离质谱法检测遗传物质（脱氧核糖核酸，DNA）以检测已知突变，特别是单核苷酸多态性（SNP）的存在的方法。 本发明使用具有修饰位点的核苷三磷酸作为引物延伸的方法，在复制，酶促反应中和至少部分地从延伸产物中除去引物，以及通过化学处理修饰位点的产物中和，从而得到的DNA 产品可以通过使用特殊的基质材料，优选以无加合物的形式与反应溶液中的其它组分电离，而无需任何进一步的清洁。 该方法特别适用于通过复用同时鉴定几种突变。

    Method for HLA typing
    10.
    发明授权
    Method for HLA typing 有权
    HLA分型方法

    公开(公告)号：US08435740B2

    公开(公告)日：2013-05-07

    申请号：US12881867

    申请日：2010-09-14

    申请人： Ivo Glynne Gut ,  Ramon Kucharzak

    发明人： Ivo Glynne Gut ,  Ramon Kucharzak

    IPC分类号： C40B40/06

    CPC分类号： C12Q1/6881 ,  C12Q1/6827 ,  C12Q1/6872 ,  C12Q2600/156 ,  C12Q2600/172 ,  C12Q2565/627 ,  C12Q2537/143 ,  C12Q2535/125

    摘要： A method for the identification of DNA sequence elements in complex and highly variable sequences is described. The method consists of identifying a short sequence element of several DNA bases (2-6 bases) at a given position in the genome simultaneously on all parental alleles. The method allows differentiating mini-haplotypes on different alleles in one analysis. The method consists of carrying out an enzymatic primer extension reaction with a combination of extension primers (pool of primers) and analyzing the products by mass spectrometry. The pool of primers is assembled in such a way that the primer extension product allows unambiguous identification of both the primer of the pool that was extended and the base that was added. The method of great utility for DNA sequences harboring many SNP's close to each other with many possible haplotypes. Such sequences are known in the Major Histocompatibility Complex (MHC). This method is particularly well suited for DNA-based HLA typing and in combination with a suitable selection of sites tested, it is superior in ease of operation to conventional HLA typing methods. We have identified sets of these assays for HLA-A, HLA-B, and HLA-DRB 1 that allow unambiguous four-digit HLA of each of these genes with between 11 and 28 queried markers.

    摘要翻译： 描述了用于鉴定复杂和高度可变序列中的DNA序列元件的方法。 该方法包括在所有亲本等位基因中同时鉴定基因组中给定位置上几个DNA碱基（2-6个碱基）的短序列元件。 该方法允许在一个分析中区分不同等位基因上的微型单倍型。 该方法包括用扩增引物（引物库）进行酶引发延伸反应，并通过质谱分析产物。 以这样的方式组装引物池，使得引物延伸产物允许明确鉴定扩展的池的引物和所添加的碱基。 对于具有许多可能的单倍型的许多SNP彼此接近的DNA序列具有很大效用的方法。 这些序列在主要组织相容性复合体（MHC）中是已知的。 该方法特别适用于基于DNA的HLA分型，并结合适当选择的测试位点，其操作方便性优于常规HLA分型方法。 我们已经确定了HLA-A，HLA-B和HLA-DRB 1的这些测定集，这些测定允许这些基因中的每一个具有11到28个查询标记的明确的四位数HLA。