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1. 发明申请

US20120135407A1 Compositions and Methods for Intramolecular Nucleic Acid Rearrangement 有权
标题翻译：分子内核酸重排的组成和方法
公开(公告)号：US20120135407A1
公开(公告)日：2012-05-31
申请号：US13387343
申请日：2010-08-13
申请人： Sydney Brenner , Gi Mikawa , Robert Osborne , Andrew Slatter
发明人： Sydney Brenner , Gi Mikawa , Robert Osborne , Andrew Slatter
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6874 , C12N15/1065 , C12Q1/6806 , C12Q1/6855 , C12Q1/686 , C12Q2563/179 , C12Q2537/143 , C12Q2535/122 , C12Q2525/161 , C12Q2525/155 , C12Q2525/143
摘要： Aspects of the present invention are drawn to processes for moving a region of interest in a polynucleotide from a first position to a second position with regard to a domain within the polynucleotide, also referred to as a “reflex method”. In certain embodiments, the reflex method results in moving a region of interest into functional proximity to specific domain elements present in the polynucleotide (e.g., primer sites and/or MID). Compositions, kits and systems that find use in carrying out the reflex processes described herein are also provided.
摘要翻译：本发明的方面涉及将多核苷酸中的感兴趣区域从关于多核苷酸内的结构域的第一位置移动至第二位置的方法，也被称为“反射方法”。在某些实施方案中，反射方法导致将感兴趣区域移动到存在于多核苷酸（例如，引物位点和/或MID）中的特定结构域元件的功能接近。还提供了用于实施本文所述的反射过程的组合物，试剂盒和系统。

2. 发明授权

US08298767B2 Compositions and methods for intramolecular nucleic acid rearrangement 有权
标题翻译：分子内核酸重排的组合物和方法
公开(公告)号：US08298767B2
公开(公告)日：2012-10-30
申请号：US13387343
申请日：2010-08-13
申请人： Sydney Brenner , Gi Mikawa , Robert Osborne , Andrew Slatter
发明人： Sydney Brenner , Gi Mikawa , Robert Osborne , Andrew Slatter
IPC分类号： C12Q1/68 , C12P19/34 , C07H21/02 , C07H21/04
CPC分类号： C12Q1/6874 , C12N15/1065 , C12Q1/6806 , C12Q1/6855 , C12Q1/686 , C12Q2563/179 , C12Q2537/143 , C12Q2535/122 , C12Q2525/161 , C12Q2525/155 , C12Q2525/143
摘要： Aspects of the present invention are drawn to processes for moving a region of interest in a polynucleotide from a first position to a second position with regard to a domain within the polynucleotide, also referred to as a “reflex method”. In certain embodiments, the reflex method results in moving a region of interest into functional proximity to specific domain elements present in the polynucleotide (e.g., primer sites and/or MID). Compositions, kits and systems that find use in carrying out the reflex processes described herein are also provided.
摘要翻译：本发明的方面涉及将多核苷酸中的感兴趣区域从第一位置移动到第二位置的方法，该多核苷酸相对于多核苷酸内的结构域也称为反射方法。在某些实施方案中，反射方法导致将感兴趣区域移动到存在于多核苷酸（例如，引物位点和/或MID）中的特定结构域元件的功能接近。还提供了用于实施本文所述的反射过程的组合物，试剂盒和系统。

3. 发明申请

US20120245041A1 BASE-BY-BASE MUTATION SCREENING 审中-公开
标题翻译：基本的基本移植筛选
公开(公告)号：US20120245041A1
公开(公告)日：2012-09-27
申请号：US13501209
申请日：2010-10-29
申请人： Sydney Brenner , Gi Mikawa
发明人： Sydney Brenner , Gi Mikawa
IPC分类号： C40B20/04
CPC分类号： C12Q1/6827 , C12Q1/6858 , C12Q2537/1373 , C12Q2535/125 , C12Q2525/125
摘要： Aspects of the present invention are drawn to screening assays for isolating polynucleotides having a sequence variation or mutation. Embodiments of the screening assays include generating a population of polynucleotide duplexes having 5′ overhang regions on one strand of the duplex (the “template” or “bottom strand”) followed by isolating polynucleotide duplexes from the mixture that have one or more mismatched base at the 3′ end of the other strand of the duplex (the “test” or “top” strand).
摘要翻译：本发明的方面涉及用于分离具有序列变异或突变的多核苷酸的筛选试验。筛选测定的实施方案包括产生在双链体（“模板”或“底部链”）的一条链上具有5'突出端区域的多核苷酸双链体群体，随后从具有一个或多个错配碱基的混合物中分离多核苷酸双链体双链的另一条链的3'末端（“测试”或“顶部”链）。

4. 发明授权

US07368265B2 Selective genome amplification 有权
标题翻译：选择性基因组扩增
公开(公告)号：US07368265B2
公开(公告)日：2008-05-06
申请号：US11656762
申请日：2007-01-22
申请人： Sydney Brenner , Gi Mikawa , Stephen C. Macevicz
发明人： Sydney Brenner , Gi Mikawa , Stephen C. Macevicz
IPC分类号： C12P19/34
CPC分类号： C12Q1/6855 , C12P19/34 , C12Q1/6865 , C12Q2525/301 , C12Q2525/143 , C12Q2531/143
摘要： The invention provides methods and compositions for amplifying selected polynucleotides, especially selected subsets of restriction fragments. Generally, methods of the invention are implemented by ligating adaptors containing at least one promoter sequence to such fragments under conditions that promote the formation of closed single stranded or double stranded structures, which are capable of serving as cyclical templates for transcription.
摘要翻译：本发明提供用于扩增所选择的多核苷酸，特别是选择的限制性片段的亚组的方法和组合物。通常，本发明的方法通过将包含至少一个启动子序列的衔接子连接到这样的片段上，在促进形成封闭的单链或双链结构的条件下实现，所述封闭单链或双链结构能够用作转录的循环模板。

5. 发明申请

US20070190556A1 Selective genome amplification 有权
标题翻译：选择性基因组扩增
公开(公告)号：US20070190556A1
公开(公告)日：2007-08-16
申请号：US11656762
申请日：2007-01-22
申请人： Sydney Brenner , Gi Mikawa , Stephen C. Macevicz
发明人： Sydney Brenner , Gi Mikawa , Stephen C. Macevicz
IPC分类号： C12Q1/68 , C12P19/34
CPC分类号： C12Q1/6855 , C12P19/34 , C12Q1/6865 , C12Q2525/301 , C12Q2525/143 , C12Q2531/143
摘要： The invention provides methods and compositions for amplifying selected polynucleotides, especially selected subsets of restriction fragments. Generally, methods of the invention are implemented by ligating adaptors containing at least one promoter sequence to such fragments under conditions that promote the formation of closed single stranded or double stranded structures, which are capable of serving as cyclical templates for transcription.
摘要翻译：本发明提供用于扩增所选择的多核苷酸，特别是选择的限制性片段的亚组的方法和组合物。通常，本发明的方法通过将包含至少一个启动子序列的衔接子连接到这样的片段上，在促进形成封闭的单链或双链结构的条件下实现，所述封闭单链或双链结构能够用作转录的循环模板。

6. 发明申请

US20100015666A1 ISOTHERMAL DNA AMPLIFICATION 审中-公开
标题翻译：同位素DNA扩增
公开(公告)号：US20100015666A1
公开(公告)日：2010-01-21
申请号：US12501832
申请日：2009-07-13
申请人： Sydney Brenner , Gi Mikawa
发明人： Sydney Brenner , Gi Mikawa
IPC分类号： C12P19/34 , C07H21/04
CPC分类号： C12P19/34 , C12Q1/6865 , C12Q2565/537 , C12Q2525/301
摘要： The present invention provides for amplification of one or more polynucleotides by multi-staged linear amplifications using one or more RNA polymerases. At each stage RNA transcripts are accumulated at a linear rate, so that multiple stages provide for faster than linear transcript accumulation. In one aspect, the invention provides for polynucleotide amplification by ligating hairpin adaptors to an end of polynucleotides wherein the hairpin adaptors each contain a promoter sequence oriented so that transcription proceeds in the direction of the loop of the hairpin adaptor. Upon transcription through such loop region and to the complementary strand a replicate is made of the promoter sequence as well as the polynucleotide, thereby permitting exponential amplification upon reverse transcription, second strand synthesis, and repetition of the above cycle. Preferably such amplification is carried out under isothermal reaction conditions.
摘要翻译：本发明通过使用一种或多种RNA聚合酶的多级线性扩增来提供一种或多种多核苷酸的扩增。在每个阶段，RNA转录物以线性速率累积，使得多个阶段提供比线性转录物积累更快的阶段。在一个方面，本发明通过将发夹衔接子连接到多核苷酸的末端来提供多核苷酸扩增，其中发夹衔接子各自含有取向的启动子序列，使得转录沿发夹衔接子的环的方向进行。在通过这种环区转录和互补链时，由启动子序列以及多核苷酸重复，从而允许逆转录，第二链合成和上述循环的重复进行指数扩增。优选地，这种扩增在等温反应条件下进行。

7. 发明授权

US07579153B2 Isothermal DNA amplification 失效
标题翻译：等温DNA扩增
公开(公告)号：US07579153B2
公开(公告)日：2009-08-25
申请号：US11338533
申请日：2006-01-23
申请人： Sydney Brenner , Gi Mikawa
发明人： Sydney Brenner , Gi Mikawa
IPC分类号： C12Q1/68
CPC分类号： C12P19/34 , C12Q1/6865 , C12Q2565/537 , C12Q2525/301
摘要： The present invention provides for amplification of one or more polynucleotides by multi-staged linear amplifications using one or more RNA polymerases. At each stage RNA transcripts are accumulated at a linear rate, so that multiple stages provide for faster than linear transcript accumulation. In one aspect, the invention provides for polynucleotide amplification by ligating hairpin adaptors to an end of polynucleotides wherein the hairpin adaptors each contain a promoter sequence oriented so that transcription proceeds in the direction of the loop of the hairpin adaptor. Upon transcription through such loop region and to the complementary strand a replicate is made of the promoter sequence as well as the polynucleotide, thereby permitting exponential amplification upon reverse transcription, second strand synthesis, and repetition of the above cycle. Preferably such amplification is carried out under isothermal reaction conditions.
摘要翻译：本发明通过使用一种或多种RNA聚合酶的多级线性扩增来提供一种或多种多核苷酸的扩增。在每个阶段，RNA转录物以线性速率累积，使得多个阶段提供比线性转录物积累更快的阶段。在一个方面，本发明通过将发夹衔接子连接到多核苷酸的末端来提供多核苷酸扩增，其中发夹衔接子各自含有取向的启动子序列，使得转录沿发夹衔接子的环的方向进行。在通过这种环区转录和互补链时，由启动子序列以及多核苷酸重复，从而允许逆转录，第二链合成和上述循环的重复进行指数扩增。优选地，这种扩增在等温反应条件下进行。

8. 发明申请

US20060166250A1 Isothermal DNA amplification 失效
公开(公告)号：US20060166250A1
公开(公告)日：2006-07-27
申请号：US11338533
申请日：2006-01-23
申请人： Sydney Brenner , Gi Mikawa
发明人： Sydney Brenner , Gi Mikawa
IPC分类号： C12Q1/68 , C12P19/34
CPC分类号： C12P19/34 , C12Q1/6865 , C12Q2565/537 , C12Q2525/301
摘要： The present invention provides for amplification of one or more polynucleotides by multi-staged linear amplifications using one or more RNA polymerases. At each stage RNA transcripts are accumulated at a linear rate, so that multiple stages provide for faster than linear transcript accumulation. In one aspect, the invention provides for polynucleotide amplification by ligating hairpin adaptors to an end of polynucleotides wherein the hairpin adaptors each contain a promoter sequence oriented so that transcription proceeds in the direction of the loop of the hairpin adaptor. Upon transcription through such loop region and to the complementary strand a replicate is made of the promoter sequence as well as the polynucleotide, thereby permitting exponential amplification upon reverse transcription, second strand synthesis, and repetition of the above cycle. Preferably such amplification is carried out under isothermal reaction conditions.

9. 发明授权

US08481292B2 Increasing confidence of allele calls with molecular counting 有权
标题翻译：通过分子计数增加等位基因呼叫的置信度
公开(公告)号：US08481292B2
公开(公告)日：2013-07-09
申请号：US13237124
申请日：2011-09-20
申请人： James Casbon , Sydney Brenner , Robert Osborne , Conrad Lichtenstein , Andreas Claas
发明人： James Casbon , Sydney Brenner , Robert Osborne , Conrad Lichtenstein , Andreas Claas
IPC分类号： C12Q1/68 , C12P19/34 , C07H21/02 , C07H21/04 , C07H21/00
CPC分类号： C12Q1/6855 , C12N15/1065 , C12Q1/6869 , C12Q1/6886 , C12Q1/70 , G06F19/18 , C12Q2525/179 , C12Q2525/191 , C12Q2545/101
摘要： Aspects of the present invention include methods and compositions for determining the number of individual polynucleotide molecules originating from the same genomic region of the same original sample that have been sequenced in a particular sequence analysis configuration or process. In these aspects of the invention, a degenerate base region (DBR) is attached to the starting polynucleotide molecules that are subsequently sequenced (e.g., after certain process steps are performed, e.g., amplification and/or enrichment). The number of different DBR sequences present in a sequencing run can be used to determine/estimate the number of different starting polynucleotides that have been sequenced. DBRs can be used to enhance numerous different nucleic acid sequence analysis applications, including allowing higher confidence allele call determinations in genotyping applications.
摘要翻译：本发明的方面包括用于确定源自在特定序列分析配置或过程中测序的相同原始样品的相同基因组区域的单个多核苷酸分子数目的方法和组合物。在本发明的这些方面，将简并碱基区（DBR）连接到随后进行测序的起始多核苷酸分子（例如，在进行某些工艺步骤之后，例如扩增和/或富集）。存在于测序运行中的不同DBR序列的数目可用于确定/估计已测序的不同起始多核苷酸的数目。 DBR可用于增强许多不同的核酸序列分析应用，包括在基因分型应用中允许更高置信等位基因调用确定。

10. 发明申请

US20130065793A1 Methods and Compositions for Tagging and Identifying Polynucleotides 有权
公开(公告)号：US20130065793A1
公开(公告)日：2013-03-14
申请号：US13466894
申请日：2012-05-08
申请人： Sydney Brenner
发明人： Sydney Brenner
IPC分类号： C40B40/08
CPC分类号： C12Q1/6874 , C12N15/1065 , C12N15/1093 , C12P19/34 , C12Q1/6827 , C12Q1/6837 , Y10T436/143333 , C12Q2565/514 , C12Q2563/179 , C12Q2537/143 , C12Q2525/191
摘要： The invention provides methods and compositions for attaching oligonucleotide tags to polynucleotides for the purpose of carrying out analytical assays in parallel and for decoding the oligonucleotide tags of polynucleotides selected in such assays. Words, or subunits, of oligonucleotide tags index submixtures in successively more complex sets of submixtures (referred to herein as “tiers” of submixtures) that a polynucleotide goes through while successive words are added to a growing tag. By identifying each word of an oligonucleotide tag, a series of submixtures is identified including the first submixture that contains only a single polynucleotide, thereby providing the identity of the selected polynucleotide. The analysis of the words of an oligonucleotide tag can be carried out in parallel, e.g. by specific hybridization of the oligonucleotide tag to its tag complement on an addressable array; or such analysis can be carried out serially by successive specific hybridizations of labeled word complements, or the like.

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