公开(公告)号：US07785798B2

公开(公告)日：2010-08-31

申请号：US12553225

申请日：2009-09-03

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.

公开(公告)号：US08501443B2

公开(公告)日：2013-08-06

申请号：US13565105

申请日：2012-08-02

Applicant: Charles R Cantor ,  Chunming Ding

Inventor： Charles R Cantor ,  Chunming Ding

IPC: C12Q1/68 ,  C12P19/34 ,  C07H21/02

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：US07655399B2

公开(公告)日：2010-02-02

申请号：US10575119

申请日：2004-10-08

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：US08318460B2

公开(公告)日：2012-11-27

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 ,  C12P19/34 ,  C07H21/02 ,  C07H21/04

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：US08153377B2

公开(公告)日：2012-04-10

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：US09376714B2

公开(公告)日：2016-06-28

申请号：US13412984

申请日：2012-03-06

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：US20120156685A1

公开(公告)日：2012-06-21

申请号：US13412984

申请日：2012-03-06

Applicant: Charles R Cantor ,  Chunming Ding

Inventor： Charles R Cantor ,  Chunming Ding

IPC: G01N27/62

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：US07700325B2

公开(公告)日：2010-04-20

申请号：US10542043

申请日：2004-01-16

Applicant: Charles R Cantor ,  Chunming Ding

Inventor： Charles R Cantor ,  Chunming Ding

IPC: C12P19/34 ,  C12Q1/68 ,  C07H21/02

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：US07807375B2

公开(公告)日：2010-10-05

申请号：US12259376

申请日：2008-10-28

Applicant: Charles R Cantor ,  Fouad A Siddiqi

Inventor： Charles R Cantor ,  Fouad A Siddiqi

IPC: C12Q1/68

CPC classification number: C12Q1/6872 ,  C12Q2525/101 ,  C12Q2523/107

Abstract: The present invention provides a method for determining nucleic acid sequences of a template nucleic acid that requires no prior knowledge of the nucleic acid sequence present in the template nucleic acid. The method is based on combining information about the mass of a fragment, the mass of any one nucleotide and the combinations thereof, and the sequence specificity of a nucleotide cutter, either enzymatic or chemical cutter, to determine a sequence of a nucleic acid fragment. This method allows for de novo detection of sequences in a target nucleic acid without requiring any prior sequence information. This method is called Partial Sequencing by Fragmentation (PSBF) and it works by fragmenting a target into oligo- or polynucleotides whose masses or lengths are uniquely associated with known sequences. The identities of these sequences are determined solely by the specific fragmentation method used, and are always independent of the target. PSBF can be implemented using electrophoresis, mass spectrometry or any other method that can be used to distinguish the size of the cut nucleic acid sequence fragments.

Abstract translation: 本发明提供了一种确定模板核酸的核酸序列的方法，其不需要模板核酸中存在的核酸序列的先验知识。 该方法基于组合关于片段的质量，任何一个核苷酸的质量及其组合的信息以及核苷酸切割剂（酶或化学切割机）的序列特异性，以确定核酸片段的序列。 该方法允许从头检测靶核酸中的序列，而不需要任何先前的序列信息。 这种方法被称为通过片段化分段测序（PSBF），它的作用是通过将目标片段分成其质量或长度与已知序列唯一相关的寡核苷酸或多核苷酸。 这些序列的身份完全由所使用的具体碎片方法确定，并且始终与目标无关。 PSBF可以使用电泳，质谱法或可用于区分切割的核酸序列片段的大小的任何其它方法来实现。