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11. 发明申请

WO02057490A3 METHODS FOR ASSOCIATING QUANTITATIVE TRAITS WITH ALLELES IN SIBLING PAIRS 审中-公开
标题翻译：在筷子中与相关物品相关的方法
公开(公告)号：WO02057490A3
公开(公告)日：2003-07-10
申请号：PCT/US0145459
申请日：2001-10-31
申请人： CURAGEN CORP , BADER JOEL S , BANSAL ARUNA , SHAM PAK
发明人： BADER JOEL S , BANSAL ARUNA , SHAM PAK
IPC分类号： C12Q1/68 , G06F19/18
CPC分类号： G06F19/18 , C12Q1/6827
摘要： Identifying the genetic components of complex diseases is one of the most important goals of the human genome project. These diseases and their underlying risk factors are often better described by quantitative phenotypes than by an arbitrary distinction between affected and unaffected individuals. Association studies are able to identify genetic loci contributing to these quantitative trait loci directly at the cost of requiring large population sizes. Studies of sib pair populations have been suggested to increase power when populations are stratified, and tests on pooled DNA may reduce the experimental burden, but these approaches have been analyzed primarily in the context of affected/unaffected disease phenotypes. Disclosed herein are efficient methods for QTL mapping using DNA pooled from sib pairs. A preferred test using a single set of pools is to select unrelated sibs with extreme phenotypic values, requiring a population size approximately 1.5Xlarger than for individual genotyping. A preferred strategy overall, with a population size requirement only 1.24Xlarger than for individual genotyping, is a combined test of DNA pooled according to sib-difference phenotypic values. The optimal pooling fraction is 27 % and is insensitive to all model parameters including allele frequency, inheritance mode, and the magnitude of the QTL effect.
摘要翻译：识别复杂疾病的遗传成分是人类基因组计划最重要的目标之一。这些疾病及其潜在的危险因素通常由定量表型更好地描述，而不是受影响和未受影响个体之间的任意区分。协会研究能够以需要大量人口为代价直接识别对这些数量性状基因座有贡献的遗传基因座。已经提出了同胞对群体的研究，以便在人群分层时增加权力，对合并的DNA的测试可能降低实验负担，但是这些方法主要在受影响/未受影响的疾病表型的背景下进行了分析。本文公开了使用从同胞对汇集的DNA的QTL定位的有效方法。使用单个池的优选测试是选择具有极端表型值的不相关的同胞，需要与个体基因分型相比大约1.5倍的群体大小。总体而言，人口规模要求仅比个体基因分型高1.24倍的优选策略是根据同胞差异表型值合并的DNA的综合检验。最佳合并分数为27％，对所有模型参数不敏感，包括等位基因频率，遗传模式和QTL效应的大小。

12. 发明申请

WO0129268A3 METHOD FOR IDENTIFYING INTERACTING GENE PRODUCTS 审中-公开
标题翻译：识别相互作用基因产物的方法
公开(公告)号：WO0129268A3
公开(公告)日：2002-01-31
申请号：PCT/US0041279
申请日：2000-10-18
申请人： CURAGEN CORP , BADER JOEL S
发明人： BADER JOEL S
IPC分类号： G01N33/68 , G06F19/18 , G06F19/20 , C12Q1/68 , G01N33/53
CPC分类号： G06F19/18 , G01N33/6803 , G06F19/20
摘要： Disclosed are methods for identifying interacting gene products, such as members of protein-protein complexes.
摘要翻译：公开了用于鉴定相互作用的基因产物的方法，例如蛋白质 - 蛋白质复合物的成员。

13. 发明申请

WO02090569A3 FAMILY-BASED ASSOCIATION TESTS FOR QUANTITATIVE TRAITS USING POOLED DNA 审中-公开
标题翻译：使用POOLED DNA进行定量测试的基于家族的协会测试
公开(公告)号：WO02090569A3
公开(公告)日：2003-09-12
申请号：PCT/US0214436
申请日：2002-05-07
申请人： CURAGEN CORP , BADER JOEL S , SHAM PAK
发明人： BADER JOEL S , SHAM PAK
IPC分类号： C12Q20060101 , C12Q1/00 , C12Q1/68 , G01N33/48 , G01N33/50 , G06F19/18 , G06N3/00
CPC分类号： G06F19/18
摘要： While SNP-based marker sets and population-level DNA repositories are approaching sufficient size for whole-genome association studies, individual genotyping remains very costly. Pooled DNA tests are a less costly alternative, but uncertainty about loss of power due to allele frequency measurement error and population stratification hinder their use. Here we describe how to optimize pooled tests as an explicit function of measurement error, and we present family-based tests that eliminate stratification effects. We show that identification of functional genetic variants and linked markers may be feasible with current-day instruments.
摘要翻译：虽然基于SNP的标记集和群体级DNA存储库正在接近足够大的全基因组关联研究，但个体基因分型仍然非常昂贵。联合DNA测试是一种成本较低的替代方案，但由于等位基因频率测量误差和人口分层导致的功率损失的不确定性妨碍了其使用。这里我们描述如何优化集合测试作为测量误差的显式功能，并且我们提出消除分层效应的基于家庭的测试。我们显示功能遗传变异体和连锁标记物的鉴定可能与当前的仪器是可行的。

14. 发明申请

WO03014879A3 SYSTEM AND METHOD FOR IDENTIFYING A GENETIC RISK FACTOR FOR A DISEASE OR PATHOLOGY 审中-公开
标题翻译：用于鉴定疾病或病理学的遗传风险因子的系统和方法
公开(公告)号：WO03014879A3
公开(公告)日：2003-07-31
申请号：PCT/US0225135
申请日：2002-08-08
申请人： CURAGEN CORP , BADER JOEL S , SHAM PAK
发明人： BADER JOEL S , SHAM PAK
IPC分类号： C12P19/34 , C12Q1/68 , G01N33/48 , G01N33/50 , G06F20060101 , G06F19/18 , G06F19/22
CPC分类号： G06F19/18 , G06F19/22
摘要： The invention relates to systems and methods for detecting nucleic acid molecule encoding GENE-X having nucleotide polymorphisms indicative of increased risk for DISEASE-X. The invention also relates to a method for identifying individuals who are carriers of the genetic risk factor or are at increased risk. The method includes obtaining a biological sample from an individual and testing the individual for the nucleotide polymorphism, wherein the disease risk may increase with the expression of ALLELE-X.
摘要翻译：本发明涉及用于检测编码具有指示DISEASE-X风险增加的核苷酸多态性的GENE-X的核酸分子的系统和方法。本发明还涉及用于鉴定作为遗传风险因子的携带者或处于增加的风险中的个体的方法。该方法包括从个体获得生物样品并测试个体的核苷酸多态性，其中所述疾病风险可以随着ALLELE-X的表达而增加。

15. 发明申请

WO02057490A9 METHODS FOR ASSOCIATING QUANTITATIVE TRAITS WITH ALLELES IN SIBLING PAIRS 审中-公开
标题翻译：使同胞对中的定量性状与等位基因相关联的方法
公开(公告)号：WO02057490A9
公开(公告)日：2002-12-05
申请号：PCT/US0145459
申请日：2001-10-31
申请人： CURAGEN CORP , BADER JOEL S , BANSAL ARUNA , SHAM PAK
发明人： BADER JOEL S , BANSAL ARUNA , SHAM PAK
IPC分类号： C12Q1/68 , G06F19/18
CPC分类号： G06F19/18 , C12Q1/6827
摘要： Identifying the genetic components of complex diseases is one of the most important goals of the human genome project. These diseases and their underlying risk factors are often better described by quantitative phenotypes than by an arbitrary distinction between affected and unaffected individuals. Association studies are able to identify genetic loci contributing to these quantitative trait loci directly at the cost of requiring large population sizes. Studies of sib pair populations have been suggested to increase power when populations are stratified, and tests on pooled DNA may reduce the experimental burden, but these approaches have been analyzed primarily in the context of affected/unaffected disease phenotypes. Disclosed herein are efficient methods for QTL mapping using DNA pooled from sib pairs. A preferred test using a single set of pools is to select unrelated sibs with extreme phenotypic values, requiring a population size approximately 1.5Xlarger than for individual genotyping. A preferred strategy overall, with a population size requirement only 1.24Xlarger than for individual genotyping, is a combined test of DNA pooled according to sib-difference phenotypic values. The optimal pooling fraction is 27 % and is insensitive to all model parameters including allele frequency, inheritance mode, and the magnitude of the QTL effect.
摘要翻译：确定复杂疾病的遗传组成是人类基因组计划的最重要目标之一。这些疾病及其潜在的风险因素往往较好地通过定量表型来描述，而不是受影响和未受影响的个体之间的任意区分。关联研究能够以需要大量种群大小为代价直接鉴定对这些数量性状基因座有贡献的基因位点。已经建议对同胞对群体进行研究以在群体分层时增加能力，并且对汇集的DNA进行测试可以减少实验负担，但是这些方法主要在受影响/未受影响的疾病表型的情况下进行分析。本文公开了使用从同胞对合并的DNA进行QTL作图的有效方法。使用单组池的优选测试是选择具有极端表型值的不相关同胞，需要比单个基因分型大约1.5倍的群体大小。总体而言，优选策略的群体规模仅为单个基因分型的1.24倍，是根据同胞差异表型值汇集的DNA的组合测试。最佳汇集分数为27％，对所有模型参数（包括等位基因频率，遗传模式和QTL效应的大小）不敏感。

16. 发明申请

WO0138580A9 NUCLEIC ACID PROBE ARRAYS 审中-公开
标题翻译：核酸探针阵列
公开(公告)号：WO0138580A9
公开(公告)日：2002-12-05
申请号：PCT/US0032131
申请日：2000-11-27
申请人： CURAGEN CORP , ROTHBERG JONATHAN M , BADER JOEL S
发明人： ROTHBERG JONATHAN M , BADER JOEL S
IPC分类号： G01N33/53 , C12M1/00 , C12N15/09 , C12Q1/48 , C12Q1/68 , G01N33/566 , G01N37/00
CPC分类号： B82Y30/00 , C12Q1/682 , C12Q1/6853 , C12Q2600/156 , C12Q2565/519 , C12Q2531/125 , C12Q2521/501
摘要： Disclosed are nucleic acid probe arrays and methods of identifying and sequencing nucleic acids in a population of nucleic acids using the arrays. The method is preferably performed by annealing a nucleic acid template to an anchor primer attached to a durface of the array. At least one anchor in the array has a sequence complementary to sequences at the 5' and 3' termini of a target nucleic acid.The annealed linear target nucleic acid is circularized using one or two ligation reactions. In one embodiment, one liggation is issued. Annealing of of the linear nucleic acid results in juxtaposition of the 5' and 3' termini of the target nucleic acid on the anchor primer. Addition of a ligase results in circulization of the target nucleic acid. This circularized nucleic acid is a template for extension of the anchor primer in a rolling circle amplification reaction. An extended anchor primer containing multiple copies of a sequence complementary to the circular mucleic acid is also referred to herein as a anchor primer nucleid acid-nucleic acid concatamer. The presence of multiple copies of the complementary sequence facilitates detection of the nucleic acid. Thus, the method provides for a highly sensitive method of detecting a desired nucleic acid attached at a discrete location on the array.
摘要翻译：公开了核酸探针阵列和使用阵列鉴定和测序核酸群体中的核酸的方法。该方法优选通过将核酸模板退火至连接到阵列的表面的锚定引物进行。阵列中的至少一个锚具有与靶核酸的5'和3'末端的序列互补的序列。退火的线性靶核酸使用一个或两个连接反应进行环化。在一个实施例中，发出一次结扎。线性核酸的退火导致靶核酸的5'和3'末端在锚定引物上并列。连接酶的加入导致靶核酸的循环。该循环核酸是用于在滚环扩增反应中延伸锚定引物的模板。包含与环状核酸互补的多个拷贝的扩增的锚定引物在本文中也称为锚定引物核酸 - 核酸连接体。互补序列的多拷贝的存在便于检测核酸。因此，该方法提供了检测在阵列上离散位置附着的所需核酸的高灵敏度方法。

17. 发明申请

WO0138580A2 NUCLEIC ACID PROBE ARRAYS 审中-公开
标题翻译：核酸探针阵列
公开(公告)号：WO0138580A2
公开(公告)日：2001-05-31
申请号：PCT/US0032131
申请日：2000-11-27
申请人： CURAGEN CORP , ROTHBERG JONATHAN M , BADER JOEL S
发明人： ROTHBERG JONATHAN M , BADER JOEL S
IPC分类号： G01N33/53 , C12M1/00 , C12N15/09 , C12Q1/48 , C12Q1/68 , G01N33/566 , G01N37/00
CPC分类号： B82Y30/00 , C12Q1/682 , C12Q1/6853 , C12Q2600/156 , C12Q2565/519 , C12Q2531/125 , C12Q2521/501
摘要： Disclosed are nucleic acid probe arrays and methods of identifying and sequencing nucleic acids in a population of nucleic acids using the arrays.
摘要翻译：公开了核酸探针阵列和使用阵列鉴定和测序核酸群体中的核酸的方法。

18. 发明申请

WO0036407A9 SEPARATION OF CHARGED PARTICLES BY A SPATIALLY AND TEMPORALLY VARYING ELECTRIC FIELD 审中-公开
标题翻译：用时空电场分离带电粒子
公开(公告)号：WO0036407A9
公开(公告)日：2000-12-07
申请号：PCT/US9929195
申请日：1999-12-09
申请人： CURAGEN CORP
发明人： BADER JOEL S , ROTHBERG JONATHAN M , DEEM MICHAEL W , MULHERN GREGORY T , WENT GREGORY T , SIMPSON JOHN , HENCK STEVEN
IPC分类号： B01D57/02 , C12M1/00 , C12N15/09 , C12Q1/68 , G01N27/26 , G01N27/447 , G01N33/483 , G01N33/50 , G01N37/00
CPC分类号： B82Y30/00 , G01N27/44773
摘要： This invention relates to a method and device for separating particles according to their diffusivities in a separation medium by means of a spatially and temporally varying electric potential. The method takes advantage of the transport of charged particles subject to an electric potential that is cycled between an off-state (in which the potential is flat) and one or more on-states, in which the potential is preferably spatially periodic with a plurality of eccentrically shaped stationary wells. The potential wells are at a constant spatial positions in the on-state. Differences in liquid-phase diffusivities lead to charged particle separation. A separation medium fills physically defined separation lanes (15) in the device. Electrodes deposited substantially transverse to the lanes create the required potential. Advantageously, injection ports (16) allow sample loading, and special gating electrodes focus the sample prior to separation.
摘要翻译：本发明涉及用于借助于空间和时间变化的电势根据其在分离介质中的扩散性来分离颗粒的方法和设备。该方法利用带电粒子的输送，该输送受到在断开状态（其中电位是平坦的）和一个或多个导通状态之间循环的电势的影响，其中电势优选地在空间上与多个偏心的固定井。势阱在导通状态下处于恒定的空间位置。液相扩散率的差异导致带电粒子分离。分离介质填充设备中物理限定的分离通道（15）。基本上横向于通道沉积的电极产生所需的电势。有利的是，注入口（16）允许样品加载，并且特殊的选通电极在分离前聚焦样品。

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