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    Accelerating identification of single nucleotide polymorphisms and alignment of clones in genomic sequencing
    1.
    发明授权
    Accelerating identification of single nucleotide polymorphisms and alignment of clones in genomic sequencing 有权
    加速单核苷酸多态性的鉴定和基因组测序中克隆的比对

    公开(公告)号：US06534293B1

    公开(公告)日：2003-03-18

    申请号：US09478189

    申请日：2000-01-05

    申请人： Francis Barany ,  Jianzhao Liu ,  Brian W. Kirk ,  Monib Zirvi ,  Norman P. Gerry ,  Philip B. Paty

    发明人： Francis Barany ,  Jianzhao Liu ,  Brian W. Kirk ,  Monib Zirvi ,  Norman P. Gerry ,  Philip B. Paty

    IPC分类号： C12P1934

    CPC分类号： C12Q1/6827 ,  C12Q1/6837 ,  C12Q1/6841 ,  C12Q1/6855 ,  C12Q1/6874 ,  Y10T436/143333 ,  C12Q2525/155 ,  C12Q2521/301 ,  C12Q2539/107 ,  C12Q2535/113 ,  C12Q2525/191 ,  C12Q2565/501 ,  C12Q2561/125 ,  C12Q2565/514

    摘要： The present invention is directed to a method of assembling genomic maps of an organism's DNA or portions thereof. A library of an organism's DNA is provided where the individual genomic segments or sequences are found on more than one clone in the library. Representations of the genome are created, and nucleic acid sequence information is generated from the representations. The sequence information is analyzed to determine clone overlap from a representation. The clone overlap and sequence information from different representations is combined to assemble a genomic map of the organism. Once the genomic map is obtained, genomic sequence information from multiple individuals can be applied to the map and compared with one another to identify single nucleotide polymorphisms. These single nucleotide polymorphisms can be detected, and alleles quantified, by conducting (1) a global PCR amplification which creates a genome representation, and (2) a ligation detection reaction process whose ligation products are captured by hybridization to a support.

    摘要翻译： 本发明涉及一种组装生物体DNA或其部分的基因组图谱的方法。 提供了生物体DNA的文库，其中在文库中的多于一个克隆上发现各个基因组片段或序列。 创建基因组的表示，并从表示生成核酸序列信息。 分析序列信息以从表示确定克隆重叠。 来自不同表示的克隆重叠和序列信息被组合以组装生物体的基因组图。 一旦得到基因组图谱，可以将多个个体的基因组序列信息应用于该图并相互比较以鉴定单核苷酸多态性。 通过进行（1）产生基因组表达的全局PCR扩增，以及（2）通过与载体杂交捕获其连接产物的连接检测反应过程，可以检测这些单核苷酸多态性和等位基因进行定量。

    Method of designing addressable array suitable for detection of nucleic acid sequence differences using ligase detection reaction
    3.
    发明授权
    Method of designing addressable array suitable for detection of nucleic acid sequence differences using ligase detection reaction 有权
    使用连接酶检测反应设计适用于检测核酸序列差异的可寻址阵列的方法

    公开(公告)号：US08492085B2

    公开(公告)日：2013-07-23

    申请号：US12252169

    申请日：2008-10-15

    申请人： Francis Barany ,  Monib Zirvi ,  Norman P. Gerry ,  Reyna Favis ,  Richard Kliman

    发明人： Francis Barany ,  Monib Zirvi ,  Norman P. Gerry ,  Reyna Favis ,  Richard Kliman

    IPC分类号： C12Q1/68 ,  C12M1/00 ,  C12M1/34 ,  C12M3/00

    CPC分类号： C12Q1/6837 ,  C12Q1/6827 ,  C12Q1/6874 ,  C12Q1/6886 ,  C12Q2527/107 ,  C12Q2521/501 ,  C12Q2521/319 ,  C12Q2565/501

    摘要： The present invention is directed to a method of designing a plurality of capture oligonucleotide probes for use on a support to which complementary oligonucleotide probes will hybridize with little mismatch, where the plural capture oligonucleotide probes have melting temperatures within a narrow range. The first step of the method involves providing a first set of a plurality of tetramers of four nucleotides linked together, where (1) each tetramer within the first set differs from all other tetramers in the first set by at least two nucleotide bases, (2) no two tetramers within the first set are complementary to one another, (3) no tetramers within the first set are palindromic or dinucleotide repeats, and (4) no tetramer within the first set has one or less or three or more G or C nucleotides. Groups of 2 to 4 of the tetramers from the first set are linked together to form a collection of multimer units. From the collection of multimer units, all multimer units formed from the same tetramer and all multimer units having a melting temperature in .degree. C. of less than 4 times the number of tetramers forming a multimer unit are removed to form a modified collection of multimer units. The modified collection of multimer units is arranged in a list in order of melting temperature. The order of the modified collection of multimer units is randomized in 2.degree. C. increments of melting temperature.

    摘要翻译： 本发明涉及一种设计多个捕获寡核苷酸探针的方法，所述多个捕获寡核苷酸探针用于互补寡核苷酸探针与少量错配杂交的载体上，其中多个捕获寡核苷酸探针具有在窄范围内的熔融温度。 该方法的第一步涉及提供连接在一起的四个核苷酸的多个四聚体的第一组，其中（1）第一组中的每个四聚体与第一组中的所有其它四聚体相差至少两个核苷酸碱基（2 ）第一组中没有两个四聚体彼此互补，（3）第一组中没有四聚体是回文或二核苷酸重复，和（4）第一组中没有四聚体具有一个或更少或三个或更多个G或C 核苷酸。 来自第一组的4至4个四聚体的组连接在一起以形成多聚体单元的集合。 从多聚体单元的收集中，由相同四聚体形成的所有多聚体单元和具有等温熔融温度的所有多聚体单元。 去除形成多聚体单元的四聚体数目的小于4倍的C.形成多聚体单元的修改的集合。 修改的多聚体单元的集合按照熔融温度的顺序排列在列表中。 修饰的多聚体单位收集的顺序是随机分为2度。 C.熔化温度升高。

    Method of designing addressable array for detection of nucleic acid sequence differences using ligase detection reaction
    4.
    发明授权
    Method of designing addressable array for detection of nucleic acid sequence differences using ligase detection reaction 有权
    使用连接酶检测反应设计用于检测核酸序列差异的可寻址阵列的方法

    公开(公告)号：US07455965B2

    公开(公告)日：2008-11-25

    申请号：US10257158

    申请日：2001-04-04

    申请人： Francis Barany ,  Monib Zirvi ,  Norman P. Gerry ,  Reyna Favis ,  Richard Kliman

    发明人： Francis Barany ,  Monib Zirvi ,  Norman P. Gerry ,  Reyna Favis ,  Richard Kliman

    IPC分类号： C12Q1/68 ,  C12P19/34

    CPC分类号： C12Q1/6837 ,  C12Q1/6827 ,  C12Q1/6874 ,  C12Q1/6886 ,  C12Q2527/107 ,  C12Q2521/501 ,  C12Q2521/319 ,  C12Q2565/501

    摘要： The present invention is directed to a method of designing a plurality of capture oligonucleotide probes for use on a support to which complementary oligonucleotide probes will hybridize with little mismatch, where the plural capture oligonucleotide probes have melting temperatures within a narrow range. The first step of the method involves providing a first set of a plurality of tetramers of four nucleotides linked together, where (1) each tetramer within the first set differs from all other tetramers in the first set by at least two nucleotide bases, (2) no two tetramers within the first set are complementary to one another, (3) no tetramers within the first set are palindromic or dinucleotide repeats, and (4) no tetramer within the first set has one or less or three or more G or C nucleotides. Groups of 2 to 4 of the tetramers from the first set are linked together to form a collection of multimer units. From the collection of multimer units, all multimer units formed from the same tetramer and all multimer units having a melting temperature in ° C. of less than 4 times the number of tetramers forming a multimer unit are removed to form a modified collection of multimer units. The modified collection of multimer units is arranged in a list in order of melting temperature. The order of the modified collection of multimer units is randomized in 2° C. increments of melting temperature.

    摘要翻译： 本发明涉及一种设计多个捕获寡核苷酸探针的方法，所述多个捕获寡核苷酸探针用于互补寡核苷酸探针与少量错配杂交的载体上，其中多个捕获寡核苷酸探针具有在窄范围内的熔融温度。 该方法的第一步涉及提供连接在一起的四个核苷酸的多个四聚体的第一组，其中（1）第一组中的每个四聚体与第一组中的所有其它四聚体相差至少两个核苷酸碱基（2 ）第一组中没有两个四聚体彼此互补，（3）第一组中没有四聚体是回文或二核苷酸重复，和（4）第一组中没有四聚体具有一个或更少或三个或更多个G或C 核苷酸。 来自第一组的4至4个四聚体的组连接在一起以形成多聚体单元的集合。 从多聚体单元的收集中，除去由相同的四聚体形成的所有多聚体单元和具有小于形成多聚体单元的四聚体数目的4倍的熔点在℃℃的所有多聚体单元以形成多聚体单元的修饰的聚集体 。 修改的多聚体单元的集合按照熔融温度的顺序排列在列表中。 修改的多聚体单元收集的顺序在2℃的熔融温度增量下随机化。