公开(公告)号：US08706422B2

公开(公告)日：2014-04-22

申请号：US12178116

申请日：2008-07-23

申请人： Yuk-Ming Dennis Lo ,  Rossa Wai Kwun Chiu ,  Kwan Chee Chan ,  Benny Chung Ying Zee ,  Ka Chun Chong

发明人： Yuk-Ming Dennis Lo ,  Rossa Wai Kwun Chiu ,  Kwan Chee Chan ,  Benny Chung Ying Zee ,  Ka Chun Chong

IPC分类号： G01N33/50 ,  G01N33/48

CPC分类号： C12Q1/6883 ,  C12Q1/6827 ,  C12Q1/6888 ,  C12Q2600/112 ,  C12Q2600/154 ,  C12Q2600/156 ,  G01N2800/387 ,  G06F19/18 ,  G06F19/22 ,  C12Q2521/331 ,  C12Q2537/16

摘要： Methods, systems, and apparatus are provided for determining whether a nucleic acid sequence imbalance exists within a biological sample. One or more cutoff values for determining an imbalance of, for example, the ratio of the two sequences (or sets of sequences) are chosen. The cutoff value may be determined based at least in part on the percentage of fetal DNA in a sample, such as maternal plasma, containing a background of maternal nucleic acid sequences. The cutoff value may also be determined based on an average concentration of a sequence per reaction. In one aspect, the cutoff value is determined from a proportion of informative wells that are estimated to contain a particular nucleic acid sequence, where the proportion is determined based on the above-mentioned percentage and/or average concentration. The cutoff value may be determined using many different types of methods, such as sequential probability ratio testing (SPRT).

摘要翻译： 提供了用于确定生物样品中是否存在核酸序列不平衡的方法，系统和装置。 选择用于确定例如两个序列（或序列集合）的比例的不平衡的一个或多个截断值。 截止值可以至少部分地基于含有母体核酸序列背景的样品中的胎儿DNA（例如母体血浆）的百分比来确定。 截止值也可以基于每个反应的序列的平均浓度来确定。 在一个方面，截断值由估计含有特定核酸序列的信息井的比例确定，其中所述比例基于上述百分比和/或平均浓度来确定。 截断值可以使用许多不同类型的方法来确定，例如顺序概率比测试（SPRT）。

公开(公告)号：US20090087847A1

公开(公告)日：2009-04-02

申请号：US12178116

申请日：2008-07-23

申请人： Yuk-Ming Dennis LO ,  Rossa Wai Kwun Chiu ,  Kwan Chee Chan ,  Benny Chung Ying Zee ,  Ka Chun Chong

发明人： Yuk-Ming Dennis LO ,  Rossa Wai Kwun Chiu ,  Kwan Chee Chan ,  Benny Chung Ying Zee ,  Ka Chun Chong

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6883 ,  C12Q1/6827 ,  C12Q1/6888 ,  C12Q2600/112 ,  C12Q2600/154 ,  C12Q2600/156 ,  G01N2800/387 ,  G06F19/18 ,  G06F19/22 ,  C12Q2521/331 ,  C12Q2537/16

摘要： Methods, systems, and apparatus are provided for determining whether a nucleic acid sequence imbalance exists within a biological sample. One or more cutoff values for determining an imbalance of, for example, the ratio of the two sequences (or sets of sequences) are chosen. The cutoff value may be determined based at least in part on the percentage of fetal DNA in a sample, such as maternal plasma, containing a background of maternal nucleic acid sequences. The cutoff value may also be determined based on an average concentration of a sequence per reaction. In one aspect, the cutoff value is determined from a proportion of informative wells that are estimated to contain a particular nucleic acid sequence, where the proportion is determined based on the above-mentioned percentage and/or average concentration. The cutoff value may be determined using many different types of methods, such as sequential probability ratio testing (SPRT).

摘要翻译： 提供了用于确定生物样品中是否存在核酸序列不平衡的方法，系统和装置。 选择用于确定例如两个序列（或序列集合）的比例的不平衡的一个或多个截断值。 截止值可以至少部分地基于含有母体核酸序列背景的样品中的胎儿DNA（例如母体血浆）的百分比来确定。 截止值也可以基于每个反应的序列的平均浓度来确定。 在一个方面，截断值由估计含有特定核酸序列的信息井的比例确定，其中所述比例基于上述百分比和/或平均浓度来确定。 截断值可以使用许多不同类型的方法来确定，例如顺序概率比测试（SPRT）。

公开(公告)号：US12065704B2

公开(公告)日：2024-08-20

申请号：US13070251

申请日：2011-03-23

申请人： Yuk-Ming Dennis Lo ,  Rossa Wai Kwun Chiu ,  Kwan Chee Chan

发明人： Yuk-Ming Dennis Lo ,  Rossa Wai Kwun Chiu ,  Kwan Chee Chan

IPC分类号： C12Q1/6886 ,  C12Q1/6809 ,  C12Q1/6827 ,  C12Q1/6874 ,  C12Q1/6883 ,  G16B20/00 ,  G16B20/10 ,  G16B20/20 ,  G16B30/00 ,  G16B30/10

CPC分类号： C12Q1/6886 ,  C12Q1/6809 ,  C12Q1/6827 ,  C12Q1/6874 ,  C12Q1/6883 ,  G16B20/00 ,  G16B20/10 ,  G16B20/20 ,  G16B30/00 ,  G16B30/10 ,  C12Q2600/156 ,  C12Q1/6827 ,  C12Q2537/16

摘要： Embodiments of this invention provide methods, systems, and apparatus for determining whether a fetal chromosomal aneuploidy exists from a biological sample obtained from a pregnant female. Nucleic acid molecules of the biological sample are sequenced, such that a fraction of the genome is sequenced. Respective amounts of a clinically-relevant chromosome and of background chromosomes are determined from results of the sequencing. The determination of the relative amounts may count sequences of only certain length. A parameter derived from these amounts (e.g. a ratio) is compared to one or more cutoff values, thereby determining a classification of whether a fetal chromosomal aneuploidy exists. Prior to sequencing, the biological sample may be enriched for DNA fragments of a particular sizes.

公开(公告)号：US20140329695A1

公开(公告)日：2014-11-06

申请号：US14335374

申请日：2014-07-18

申请人： Yuk-Ming Dennis Lo ,  Rossa Wai Kwun Chiu ,  Kwan Chee Chan

发明人： Yuk-Ming Dennis Lo ,  Rossa Wai Kwun Chiu ,  Kwan Chee Chan

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6883 ,  C12Q1/6827 ,  C12Q1/6888 ,  C12Q2600/112 ,  C12Q2600/154 ,  C12Q2600/156 ,  G01N2800/387 ,  G06F19/18 ,  G06F19/22 ,  C12Q2521/331 ,  C12Q2537/16

摘要： Embodiments of this invention provide methods, systems, and apparatus for determining whether a fetal chromosomal aneuploidy exists from a biological sample obtained from a pregnant female. Nucleic acid molecules of the biological sample are sequenced, such that a fraction of the genome is sequenced. Respective amounts of a clinically-relevant chromosome and of background chromosomes are determined from results of the sequencing. A parameter derived from these amounts (e.g. a ratio) is compared to one or more cutoff values, thereby determining a classification of whether a fetal chromosomal aneuploidy exists.

公开(公告)号：US08288100B2

公开(公告)日：2012-10-16

申请号：US12791776

申请日：2010-06-01

申请人： Yuk Ming Dennis Lo ,  Rossa Wai Kwun Chiu ,  Stephen Siu Chung Chim ,  Chunming Ding ,  Kwan Chee Chan ,  Hing Nam Ivy Wong ,  Ka Chun Ryan Yuen

发明人： Yuk Ming Dennis Lo ,  Rossa Wai Kwun Chiu ,  Stephen Siu Chung Chim ,  Chunming Ding ,  Kwan Chee Chan ,  Hing Nam Ivy Wong ,  Ka Chun Ryan Yuen

IPC分类号： C12Q1/68 ,  C07H21/02 ,  C07H21/04

CPC分类号： C12Q1/68 ,  C12Q1/6876 ,  C12Q1/6883 ,  C12Q2600/154 ,  C12Q2600/156

摘要： This application describes the discovery that, in a pregnant woman, certain genes (such as RASSF1A, APC, CASP8, RARB, SCGB3A1, DAB2IP, PTPN6, THY1, TMEFF2, and PYCARD) originated from a fetus are highly methylated, whereas the same genes of maternal origin are unmethylated. This discovery allows the easy detection of one or more of these methylated fetal genes in a biological sample from a pregnant woman, serving as a universal indicator of the presence of fetal DNA in the sample. These fetal methylation markers are particularly useful as positive controls for a non-invasive analytical process during which the quality and quantity of fetal DNA are monitored. These newly identified fetal markers can also be measured directly for diagnosis of certain pregnancy-related conditions.

摘要翻译： 该应用描述了在孕妇中发现来自胎儿的某些基因（如RASSF1A，APC，CASP8，RARB，SCGB3A1，DAB2IP，PTPN6，THY1，TMEFF2和PYCARD）高度甲基化，而相同的基因 产妇来源是未甲基化。 该发现允许从孕妇的生物样品中容易地检测这些甲基化胎儿基因中的一种或多种，​​作为样品中胎儿DNA存在的通用指标。 这些胎儿甲基化标记物作为非侵入性分析过程的阳性对照特别有用，在此过程中监测胎儿DNA的质量和数量。 这些新确定的胎儿标记物也可以直接测量以诊断某些妊娠相关病症。

公开(公告)号：US20140256560A1

公开(公告)日：2014-09-11

申请号：US14087525

申请日：2013-11-22

申请人： Yuk-Ming Dennis Lo ,  Rossa Wai Kwun Chiu ,  Kwan Chee Chan

发明人： Yuk-Ming Dennis Lo ,  Rossa Wai Kwun Chiu ,  Kwan Chee Chan

IPC分类号： C12Q1/68

摘要： Embodiments of this invention provide methods, systems, and apparatus for determining whether a fetal chromosomal aneuploidy exists from a biological sample obtained from a pregnant female. Nucleic acid molecules of the biological sample are sequenced, such that a fraction of the genome is sequenced. Respective amounts of a clinically-relevant chromosome and of background chromosomes are determined from results of the sequencing. A parameter derived from these amounts (e.g. a ratio) is compared to one or more cutoff values, thereby determining a classification of whether a fetal chromosomal aneuploidy exists.

公开(公告)号：US20130084566A1

公开(公告)日：2013-04-04

申请号：US13618527

申请日：2012-09-14

申请人： YUK MING DENNIS LO ,  Rossa Wai Kwun Chiu ,  Stephen Siu Chung Chim ,  Chunming Ding ,  Kwan Chee Chan ,  Hing Nam Ivy Wong ,  Ka Chun Ryan Yuen

发明人： YUK MING DENNIS LO ,  Rossa Wai Kwun Chiu ,  Stephen Siu Chung Chim ,  Chunming Ding ,  Kwan Chee Chan ,  Hing Nam Ivy Wong ,  Ka Chun Ryan Yuen

IPC分类号： C12Q1/68

CPC分类号： C12Q1/68 ,  C12Q1/6876 ,  C12Q1/6883 ,  C12Q2600/154 ,  C12Q2600/156

摘要： This application describes the discovery that, in a pregnant woman, certain genes (such as RASSF1A, APC, CASP8, RARB, SCGB3A1, DAB2IP, PTPN6, THY1, TMEFF2, and PYCARD) originated from a fetus are highly methylated, whereas the same genes of maternal origin are unmethylated. This discovery allows the easy detection of one or more of these methylated fetal genes in a biological sample from a pregnant woman, serving as a universal indicator of the presence of fetal DNA in the sample. These fetal methylation markers are particularly useful as positive controls for a non-invasive analytical process during which the quality and quantity of fetal DNA are monitored. These newly identified fetal markers can also be measured directly for diagnosis of certain pregnancy-related conditions.

摘要翻译： 该应用描述了在孕妇中发现来自胎儿的某些基因（如RASSF1A，APC，CASP8，RARB，SCGB3A1，DAB2IP，PTPN6，THY1，TMEFF2和PYCARD）高度甲基化，而相同的基因 产妇来源是未甲基化。 该发现允许从孕妇的生物样品中容易地检测这些甲基化胎儿基因中的一种或多种，​​作为样品中胎儿DNA存在的通用指标。 这些胎儿甲基化标记物作为非侵入性分析过程的阳性对照特别有用，在此过程中监测胎儿DNA的质量和数量。 这些新确定的胎儿标记物也可以直接测量以诊断某些妊娠相关病症。

公开(公告)号：US20120003636A1

公开(公告)日：2012-01-05

申请号：US13070251

申请日：2011-03-23

申请人： Yuk-Ming Dennis Lo ,  Rossa Wai Kwun Chiu ,  Kwan-Chee Chan

发明人： Yuk-Ming Dennis Lo ,  Rossa Wai Kwun Chiu ,  Kwan-Chee Chan

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6886 ,  C12Q1/6809 ,  C12Q1/6827 ,  C12Q1/6874 ,  C12Q1/6883 ,  C12Q2600/156 ,  G16B20/00 ,  G16B30/00 ,  C12Q2537/16

摘要： Embodiments of this invention provide methods, systems, and apparatus for determining whether a fetal chromosomal aneuploidy exists from a biological sample obtained from a pregnant female. Nucleic acid molecules of the biological sample are sequenced, such that a fraction of the genome is sequenced. Respective amounts of a clinically-relevant chromosome and of background chromosomes are determined from results of the sequencing. The determination of the relative amounts may count sequences of only certain length. A parameter derived from these amounts (e.g. a ratio) is compared to one or more cutoff values, thereby determining a classification of whether a fetal chromosomal aneuploidy exists. Prior to sequencing, the biological sample may be enriched for DNA fragments of a particular sizes.

公开(公告)号：US20120003635A1

公开(公告)日：2012-01-05

申请号：US13070240

申请日：2011-03-23

申请人： Yuk-Ming Dennis Lo ,  Rossa Wai Kwun Chiu ,  Kwan Chee Chan

发明人： Yuk-Ming Dennis Lo ,  Rossa Wai Kwun Chiu ,  Kwan Chee Chan

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6886 ,  C12Q1/6809 ,  C12Q1/6827 ,  C12Q1/6874 ,  C12Q1/6883 ,  C12Q2600/156 ,  G16B20/00 ,  G16B30/00 ,  C12Q2537/16

摘要： Embodiments of this invention provide methods, systems, and apparatus for determining whether a fetal chromosomal aneuploidy exists from a biological sample obtained from a pregnant female. Nucleic acid molecules of the biological sample are sequenced, such that a fraction of the genome is sequenced. Respective amounts of a clinically-relevant chromosome and of background chromosomes are determined from results of the sequencing. The determination of the relative amounts may count sequences of only certain length. A parameter derived from these amounts (e.g. a ratio) is compared to one or more cutoff values, thereby determining a classification of whether a fetal chromosomal aneuploidy exists. Prior to sequencing, the biological sample may be enriched for DNA fragments of a particular sizes.

摘要翻译： 本发明的实施方案提供了用于确定从怀孕女性获得的生物样品中是否存在胎儿染色体非整倍性的方法，系统和装置。 对生物样品的核酸分子进行测序，使得对基因组的一部分进行测序。 根据测序结果确定相应量的临床相关染色体和背景染色体。 相对量的确定可以计算一定长度的序列。 将来自这些量（例如比例）的参数与一个或多个截断值进行比较，从而确定是否存在胎儿染色体非整倍性的分类。 在测序之前，生物样品可以富集特定大小的DNA片段。

公开(公告)号：US20110143342A1

公开(公告)日：2011-06-16

申请号：US12791776

申请日：2010-06-01

申请人： Yuk Ming Dennis Lo ,  Rossa Wai Kwun Chiu ,  Stephen Siu Chung Chim ,  Chunming Ding ,  Kwan Chee Chan ,  Hing Nam Ivy Wong ,  Ka Chun Ryan Yuen

发明人： Yuk Ming Dennis Lo ,  Rossa Wai Kwun Chiu ,  Stephen Siu Chung Chim ,  Chunming Ding ,  Kwan Chee Chan ,  Hing Nam Ivy Wong ,  Ka Chun Ryan Yuen

IPC分类号： C12Q1/68

CPC分类号： C12Q1/68 ,  C12Q1/6876 ,  C12Q1/6883 ,  C12Q2600/154 ,  C12Q2600/156

摘要： This application describes the discovery that, in a pregnant woman, certain genes (such as RASSF1A, APC, CASP8, RARB, SCGB3A1, DAB2IP, PTPN6, THY1, TMEFF2, and PYCARD) originated from a fetus are highly methylated, whereas the same genes of maternal origin are unmethylated. This discovery allows the easy detection of one or more of these methylated fetal genes in a biological sample from a pregnant woman, serving as a universal indicator of the presence of fetal DNA in the sample. These fetal methylation markers are particularly useful as positive controls for a non-invasive analytical process during which the quality and quantity of fetal DNA are monitored. These newly identified fetal markers can also be measured directly for diagnosis of certain pregnancy-related conditions.

摘要翻译： 该应用描述了在孕妇中发现来自胎儿的某些基因（如RASSF1A，APC，CASP8，RARB，SCGB3A1，DAB2IP，PTPN6，THY1，TMEFF2和PYCARD）高度甲基化，而相同的基因 产妇来源是未甲基化。 该发现允许从孕妇的生物样品中容易地检测这些甲基化胎儿基因中的一种或多种，​​作为样品中胎儿DNA存在的通用指标。 这些胎儿甲基化标记物作为非侵入性分析过程的阳性对照特别有用，在此过程中监测胎儿DNA的质量和数量。 这些新确定的胎儿标记物也可以直接测量以诊断某些妊娠相关病症。