公开(公告)号：US20110097712A1

公开(公告)日：2011-04-28

申请号：US12496390

申请日：2009-07-01

Applicant: Charles R. Cantor ,  Chunming Ding

Inventor： Charles R. Cantor ,  Chunming Ding

IPC: C12Q1/68

CPC classification number: C12Q1/6827 ,  C12Q2600/156 ,  C12Q2525/186 ,  C12Q2535/125 ,  C12Q2565/627 ,  C12Q2545/101

Abstract: The present invention is directed to a method for detecting and quantifying rare mutations in a nucleic acid sample. The nucleic acid molecules under investigation can be either DNA or RNA. The rare mutation can be any type of functional or non-functional nucleic acid change or mutation, such as deletion, insertion, translocation, inversion, one or more base substitution or polymorphism. Therefore, the methods of the present invention are useful in detection of rare mutations in, for example, diagnostic, prognostic and follow-up applications, when the targets are rare known nucleic acid variants mixed in with the wildtype or the more common nucleic acid variant(s).

Abstract translation: 本发明涉及一种用于检测和定量核酸样品中罕见突变的方法。 正在研究的核酸分子可以是DNA或RNA。 罕见突变可以是任何类型的功能或非功能性核酸变化或突变，例如缺失，插入，易位，反转，一个或多个碱基取代或多态性。 因此，当目标是罕见的已知的与野生型或更常见的核酸变体混合的核酸变体时，本发明的方法可用于检测例如诊断，预后和随访应用中的罕见突变 （s）。

公开(公告)号：US20120295263A1

公开(公告)日：2012-11-22

申请号：US13565105

申请日：2012-08-02

Applicant: Charles R. Cantor ,  Chunming Ding

Inventor： Charles R. Cantor ,  Chunming Ding

IPC: G01N27/62

CPC classification number: C12Q1/6827 ,  C12Q1/6858 ,  C12Q2600/156 ,  C12Q2527/137 ,  C12Q2537/143 ,  C12Q2565/627

Abstract: The present invention provides an efficient way for high throughput haplotype analysis. Several polymorphic nucleic acid markers, such as SNPs, can be simultaneously and reliably determined through multiplex PCR of single nucleic acid molecules in several parallel single molecule dilutions and the consequent statistical analysis of the results from these parallel single molecule multiplex PCR reactions results in reliable determination of haplotypes present in the subject. The nucleic acid markers can be of any distance to each other on the chromosome. In addition, an approach wherein overlapping DNA markers are analyzed can be used to link smaller haplotypes into larger haplotypes. Consequently, the invention provides a powerful new tool for diagnostic haplotyping and identifying novel haplotypes.

Abstract translation: 本发明提供了高通量单倍型分析的有效方法。 可以通过多个平行的单分子稀释物中的单个核酸分子的多重PCR来同时并可靠地测定几种多态性核酸标记，例如SNP，并且随后对来自这些平行的单分子多重PCR反应的结果的统计分析导致可靠的测定 的单倍体存在于受试者。 核酸标记在染色体上可以彼此有任何距离。 此外，分析重叠的DNA标记物的方法可用于将较小的单倍型连接到较大的单元型中。 因此，本发明为诊断单倍型和鉴定新型单体型提供了强大的新工具。

公开(公告)号：US20120225798A1

公开(公告)日：2012-09-06

申请号：US13369000

申请日：2012-02-08

Applicant: Charles R. Cantor ,  Chunming Ding ,  Yuk Ming Dennis Lo ,  Rossa Wai Kwum Chiu

Inventor： Charles R. Cantor ,  Chunming Ding ,  Yuk Ming Dennis Lo ,  Rossa Wai Kwum Chiu

IPC: C40B30/10

CPC classification number: C12Q1/6881 ,  C12Q1/6872 ,  C12Q2600/156 ,  C12Q2600/172 ,  C12Q2535/125

Abstract: The present invention is directed to methods of detecting nucleic acids in a biological sample. The method is based on a novel combination of a base extension reaction, which provides excellent analytical specificity, and a mass spectrometric analysis, which provides excellent specificity. The method can be used, for example, for diagnostic, prognostic and treatment purposes. The method allows accurate detection of nucleic acids that are present in very small amounts in a biological sample. For example, the method of the present invention is preferably used to detect fetal nucleic acid in a maternal blood sample; circulating tumor-specific nucleic acids in a blood, urine or stool sample; and donor-specific nucleic acids in transplant recipients. In another embodiment, one can detect viral, bacterial, fungal, or other foreign nucleic acids in a biological sample.

Abstract translation: 本发明涉及检测生物样品中核酸的方法。 该方法基于提供优异分析特异性的碱基延伸反应和提供优异特异性的质谱分析的新型组合。 该方法可用于例如诊断，预后和治疗目的。 该方法允许精确检测在生物样品中以非常少的量存在的核酸。 例如，本发明的方法优选用于检测母体血液样品中的胎儿核酸; 在血液，尿液或粪便样品中循环肿瘤特异性核酸; 和供体特异性核酸。 在另一个实施方案中，可以检测生物样品中的病毒，细菌，真菌或其它外来核酸。

公开(公告)号：US07709262B2

公开(公告)日：2010-05-04

申请号：US10589709

申请日：2005-02-18

Applicant: Charles R. Cantor ,  Chunming Ding

Inventor： Charles R. Cantor ,  Chunming Ding

IPC: C12Q1/68 ,  C12P19/34

CPC classification number: C12Q1/6827 ,  C12Q2600/156 ,  C12Q2525/186 ,  C12Q2535/125 ,  C12Q2565/627 ,  C12Q2545/101

Abstract: The present invention is directed to a method for detecting and quantifying rare mutations in a nucleic acid sample. The nucleic acid molecules under investigation can be either DNA or RNA. The rare mutation can be any type of functional or non-functional nucleic acid change or mutation, such as deletion, insertion, translocation, inversion, one or more base substitution or polymorphism. Therefore, the methods of the present invention are useful in detection of rare mutations in, for example, diagnostic, prognostic and follow-up applications, when the targets are rare known nucleic acid variants mixed in with the wildtype or the more common nucleic acid variant(s).

Abstract translation: 本发明涉及一种用于检测和定量核酸样品中罕见突变的方法。 正在研究的核酸分子可以是DNA或RNA。 罕见突变可以是任何类型的功能或非功能性核酸变化或突变，例如缺失，插入，易位，反转，一个或多个碱基取代或多态性。 因此，当目标是罕见的已知的与野生型或更常见的核酸变体混合的核酸变体时，本发明的方法可用于检测例如诊断，预后和随访应用中的罕见突变 （s）。

公开(公告)号：US08304194B2

公开(公告)日：2012-11-06

申请号：US13223923

申请日：2011-09-01

Applicant: Charles R. Cantor ,  Chunming Ding

Inventor： Charles R. Cantor ,  Chunming Ding

IPC: C12Q1/68 ,  C12P19/34

CPC classification number: C12Q1/6851 ,  C12Q2545/107 ,  C12Q2535/125 ,  C12Q2525/186

Abstract: The present invention relates to a method for measuring the amount of a target nucleic acid in a sample using a standard which is designed to have one base difference compared with the gene of interest or a “target nucleic acid sequence.” Use of such standard in combination with a method of “enhancing” the difference in the standard and the test nucleic acid sample using, for example, a base extension reaction carried right at the mutation site allowing amplification of the standard and target nucleic acids with the same efficiency and facilitating quantification of the target nucleic acid. Thereafter a means of quantifying the “enhanced” standard and target nucleic acid samples is used to determine the amount of the target nucleic acid. In the preferred embodiment, the quantification means is Mass Spectrometry.

Abstract translation: 本发明涉及使用与目标基因或靶核酸序列相比设计为具有一个碱基差异的标准物来测量样品中靶核酸量的方法。 使用这种标准物与增加标准差和测试核酸样品的方法的方法结合使用例如在突变位点上携带的碱基延伸反应，允许以相同的效率扩增标准品和靶核酸 并促进靶核酸的定量。 此后，使用量化增强的标准和靶核酸样品的方法来确定靶核酸的量。 在优选实施方案中，定量方法是质谱法。

公开(公告)号：US20110244451A1

公开(公告)日：2011-10-06

申请号：US12844058

申请日：2010-07-27

Applicant: Charles R. Cantor ,  Chunming Ding

Inventor： Charles R. Cantor ,  Chunming Ding

IPC: C12Q1/68

CPC classification number: C12Q1/6883 ,  C12Q1/6806 ,  C12Q1/6827 ,  C12Q1/6876 ,  C12Q2600/154 ,  C12Q2600/156 ,  C12Q2600/166 ,  C12Q2521/331

Abstract: Chromosomal abnormalities are responsible for a significant number of birth defects, including mental retardation. The present invention is related to methods for non-invasive and rapid, prenatal diagnosis of chromosomal abnormalities based on analysis of a maternal blood sample. The invention exploits the differences in DNA between the mother and fetus, for instance differences in their methylation states, as a means to enrich for fetal DNA in maternal plasma sample. The methods described herein can be used to detect chromosomal DNA deletions and duplications. In a preferred embodiment, the methods are used to diagnose chromosomal aneuploidy and related disorders, such as Down's and Turner's Syndrome.

Abstract translation: 染色体异常负责大量的出生缺陷，包括精神发育迟滞。 本发明涉及基于母体血液样品分析的非侵入性和快速，产前诊断染色体异常的方法。 本发明利用母体和胎儿之间的DNA差异，例如甲基化状态的差异，作为富集母体血浆样品中胎儿DNA的手段。 本文描述的方法可用于检测染色体DNA缺失和重复。 在优选的实施方案中，所述方法用于诊断染色体非整倍体和相关疾病，例如唐氏和特纳综合征。

公开(公告)号：US20090325232A1

公开(公告)日：2009-12-31

申请号：US12553225

申请日：2009-09-03

Applicant: Charles R. Cantor ,  Chunming Ding

Inventor： Charles R. Cantor ,  Chunming Ding

IPC: C12P19/30

CPC classification number: C12Q1/6883 ,  C12Q1/6806 ,  C12Q1/6827 ,  C12Q1/6876 ,  C12Q2600/154 ,  C12Q2600/156 ,  C12Q2600/166 ,  C12Q2521/331

Abstract: Chromosomal abnormalities are responsible for a significant number of birth defects, including mental retardation. The present invention is related to methods for non-invasive and rapid, prenatal diagnosis of chromosomal abnormalities based on analysis of a maternal blood sample. The invention exploits the differences in DNA between the mother and fetus, for instance differences in their methylation states, as a means to enrich for fetal DNA in maternal plasma sample. The methods described herein can be used to detect chromosomal DNA deletions and duplications. In a preferred embodiment, the methods are used to diagnose chromosomal aneuploidy and related disorders, such as Down's and Turner's Syndrome.

Abstract translation: 染色体异常负责大量的出生缺陷，包括精神发育迟滞。 本发明涉及基于母体血液样品分析的非侵入性和快速，产前诊断染色体异常的方法。 本发明利用母体和胎儿之间的DNA差异，例如甲基化状态的差异，作为富集母体血浆样品中胎儿DNA的手段。 本文描述的方法可用于检测染色体DNA缺失和重复。 在优选的实施方案中，所述方法用于诊断染色体非整倍体和相关疾病，例如唐氏和特纳综合征。

公开(公告)号：US08034567B2

公开(公告)日：2011-10-11

申请号：US10655762

申请日：2003-09-05

Applicant: Charles R. Cantor ,  Chunming Ding

Inventor： Charles R. Cantor ,  Chunming Ding

IPC: C12Q1/68 ,  C12P19/34 ,  H01J49/00 ,  H01J49/40

CPC classification number: C12Q1/6851 ,  C12Q2545/107 ,  C12Q2535/125 ,  C12Q2525/186

Abstract: The present invention relates to a method for measuring the amount of a target nucleic acid in a sample using a standard which is designed to have one base difference compared with the gene of interest or a “target nucleic acid sequence.” Use of such standard in combination with a method of “enhancing” the difference in the standard and the test nucleic acid sample using, for example, a base extension reaction carried right at the mutation site allowing amplification of the standard and target nucleic acids with the same efficiency and facilitating quantification of the target nucleic acid. Thereafter a means of quantifying the “enhanced” standard and target nucleic acid samples is used to determine the amount of the target nucleic acid. In the preferred embodiment, the quantification means is Mass Spectrometry.

Abstract translation: 本发明涉及使用与目的基因相比具有一个碱基差异的标准或“靶核酸序列”来测量样品中靶核酸量的方法。使用这种标准物 结合使用例如在突变位点上携带的碱基延伸反应来“提高”标准差和测试核酸样品的方法，允许以相同的效率扩增标准品和靶核酸并促进定量 的靶核酸。 此后，使用定量“增强”标准和靶核酸样品的手段来确定靶核酸的量。 在优选实施方案中，定量方法是质谱法。

公开(公告)号：US20100184075A1

公开(公告)日：2010-07-22

申请号：US12704043

申请日：2010-02-11

Applicant: Charles R. Cantor ,  Chunming Ding

Inventor： Charles R. Cantor ,  Chunming Ding

IPC: C12Q1/68

CPC classification number: C12Q1/6827 ,  C12Q1/6858 ,  C12Q2600/156 ,  C12Q2527/137 ,  C12Q2537/143 ,  C12Q2565/627

Abstract: The present invention provides an efficient way for high throughput haplotype analysis. Several polymorphic nucleic acid markers, such as SNPs, can be simultaneously and reliably determined through multiplex PCR of single nucleic acid molecules in several parallel single molecule dilutions and the consequent statistical analysis of the results from these parallel single molecule multiplex PCR reactions results in reliable determination of haplotypes present in the subject. The nucleic acid markers can be of any distance to each other on the chromosome. In addition, an approach wherein overlapping DNA markers are analyzed can be used to link smaller haplotypes into larger haplotypes. Consequently, the invention provides a powerful new tool for diagnostic haplotyping and identifying novel haplotypes.

Abstract translation: 本发明提供了高通量单倍型分析的有效方法。 可以通过多个平行的单分子稀释物中的单个核酸分子的多重PCR来同时并可靠地测定几种多态性核酸标记，例如SNP，并且随后对来自这些平行的单分子多重PCR反应的结果的统计分析导致可靠的测定 的单倍体存在于受试者。 核酸标记在染色体上可以彼此有任何距离。 此外，分析重叠的DNA标记物的方法可用于将较小的单倍型连接到较大的单元型中。 因此，本发明为诊断单倍型和鉴定新型单体型提供了强大的新工具。

公开(公告)号：US20080032287A1

公开(公告)日：2008-02-07

申请号：US10589709

申请日：2005-02-18

Applicant: Charles R. Cantor ,  Chunming Ding

Inventor： Charles R. Cantor ,  Chunming Ding

IPC: C12Q1/68

CPC classification number: C12Q1/6827 ,  C12Q2600/156 ,  C12Q2525/186 ,  C12Q2535/125 ,  C12Q2565/627 ,  C12Q2545/101

Abstract: The present invention is directed to a method for detecting and quantifying rare mutations in a nucleic acid sample. The nucleic acid molecules under investigation can be either DNA or RNA. The rare mutation can be any type of functional or non-functional nucleic acid change or mutation, such as deletion, insertion, translocation, inversion, one or more base substitution or polymorphism. Therefore, the methods of the present invention are useful in detection of rare mutations in, for example, diagnostic, prognostic and follow-up applications, when the targets are rare known nucleic acid variants mixed in with the wildtype or the more common nucleic acid variant(s).

Abstract translation: 本发明涉及一种用于检测和定量核酸样品中罕见突变的方法。 正在研究的核酸分子可以是DNA或RNA。 罕见突变可以是任何类型的功能或非功能性核酸变化或突变，例如缺失，插入，易位，反转，一个或多个碱基取代或多态性。 因此，当目标是罕见的已知的与野生型或更常见的核酸变体混合的核酸变体时，本发明的方法可用于检测例如诊断，预后和随访应用中的罕见突变 （s）。