公开(公告)号：US20060183128A1

公开(公告)日：2006-08-17

申请号：US10641321

申请日：2003-08-12

申请人： Kurt Berlin ,  Alexander Olek ,  Stephan Beck ,  Thomas Hildmann ,  Joern Lewin ,  Karen Novik

发明人： Kurt Berlin ,  Alexander Olek ,  Stephan Beck ,  Thomas Hildmann ,  Joern Lewin ,  Karen Novik

IPC分类号： C12Q1/68 ,  C12P19/34

CPC分类号： C12Q1/6881 ,  C12Q2600/154 ,  C12Q2600/16

摘要： The present invention provides, inter alia, a method for generating a genome-wide epigenomic map, comprising a correlation between methylation variable CpG positions (MVP) and genomic DNA sample types. MVP are those CpG positions that show a variable quantitative level of methylation between sample types. Particular genomic regions of interest (ROI) provide preferred marker sequences that comprise multiple, and preferably proximate MVP, and that have novel utility for distinguishing sample types. The epigenic maps have broad utility, for example, in identifying sample types, or for distinguishing between and among sample types. In a preferred embodiment the epigenomic map is based on methylation variable regions (MVP) within the major histocompatibility complex (MHC), and has utility, for example, in identifying the cell or tissue source of a genomic DNA sample, or for distinguishing one or more particular cell or tissue types among other cell or tissue types. Analysis of epigenetic characteristics of one, or of a set of nucleic acid sequences, in the context of an inventive epigenomic map, allows for the determination of an origin of the nucleic acids.

摘要翻译： 本发明尤其提供了一种生成全基因组表观遗传学图谱的方法，其包括甲基化可变CpG位点（MVP）和基因组DNA样品类型之间的相关性。 MVP是显示样品类型之间甲基化可变定量水平的那些CpG位置。 特定的感兴趣的基因组区域（ROI）提供优选的标记序列，其包含多个，优选接近MVP，并且具有用于区分样品类型的新颖效用。 表征性地图具有广泛的用途，例如，在识别样本类型中，或用于区分样本类型和样本类型。 在优选的实施方案中，表观基因组图基于主要组织相容性复合物（MHC）内的甲基化可变区（MVP），并且可用于例如鉴定基因组DNA样品的细胞或组织来源，或用于区分一个或 更特定的细胞或组织类型与其他细胞或组织类型。 在本发明表观遗传学图谱的上下文中，一种或一组核酸序列的表观遗传学特征的分析允许确定核酸的来源。

公开(公告)号：US20090170089A1

公开(公告)日：2009-07-02

申请号：US12036030

申请日：2008-02-22

申请人： Joern Lewin ,  Kurt Berlin ,  Thomas Hildmann ,  Alexander Olek ,  Stephan Beck ,  Karen Novik

发明人： Joern Lewin ,  Kurt Berlin ,  Thomas Hildmann ,  Alexander Olek ,  Stephan Beck ,  Karen Novik

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6881 ,  C12Q2600/154 ,  C12Q2600/16

摘要： The present invention provides, inter alia, a method for generating a genome-wide epigenomic map, comprising a correlation between methylation variable CpG positions (MVP) and genomic DNA sample types. MVP are those CpG positions that show a variable quantitative level of methylation between sample types. Particular genomic regions of interest (ROI) provide preferred marker sequences that comprise multiple, and preferably proximate MVP, and that have novel utility for distinguishing sample types. The epigenic maps have broad utility, for example, in identifying sample types, or for distinguishing between and among sample types. In a preferred embodiment the epigenomic map is based on methylation variable regions (MVP) within the major histocompatibility complex (MHC), and has utility, for example, in identifying the cell or tissue source of a genomic DNA sample, or for distinguishing one or more particular cell or tissue types among other cell or tissue types. Analysis of epigenetic characteristics of one, or of a set of nucleic acid sequences, in the context of an inventive epigenomic map, allows for the determination of an origin of the nucleic acids.

摘要翻译： 本发明尤其提供了一种生成全基因组表观遗传学图谱的方法，其包括甲基化可变CpG位点（MVP）和基因组DNA样品类型之间的相关性。 MVP是显示样品类型之间甲基化可变定量水平的那些CpG位置。 特定的感兴趣的基因组区域（ROI）提供优选的标记序列，其包含多个，优选接近MVP，并且具有用于区分样品类型的新颖效用。 表征性地图具有广泛的用途，例如，在识别样本类型中，或用于区分样本类型和样本类型。 在优选的实施方案中，表观基因组图基于主要组织相容性复合物（MHC）内的甲基化可变区（MVP），并且可用于例如鉴定基因组DNA样品的细胞或组织来源，或用于区分一个或 更特定的细胞或组织类型与其他细胞或组织类型。 在本发明表观遗传学图谱的上下文中，一种或一组核酸序列的表观遗传学特征的分析允许确定核酸的来源。

公开(公告)号：US20090191548A1

公开(公告)日：2009-07-30

申请号：US12088384

申请日：2006-09-28

申请人： Kurt Berlin ,  Stephan Beck ,  Matthias Burger ,  Rene Cortese ,  Florian Eckhardt ,  Carolina Haefliger ,  Joern Lewin ,  Fabian Model ,  Alexander Olek

发明人： Kurt Berlin ,  Stephan Beck ,  Matthias Burger ,  Rene Cortese ,  Florian Eckhardt ,  Carolina Haefliger ,  Joern Lewin ,  Fabian Model ,  Alexander Olek

IPC分类号： C12Q1/68 ,  C07H21/04

CPC分类号： C12Q1/6881 ,  C12Q2600/158

摘要： The present application provides methods and nucleic acids the classification of a biological sample. This is achieved by the analysis of the expression status of at least one of the genes selected from Table 1 as disclosed.

摘要翻译： 本申请提供了生物样品分类的方法和核酸。 通过分析所公开的选自表1中的至少一种基因的表达状态来实现。

公开(公告)号：US20110159491A1

公开(公告)日：2011-06-30

申请号：US12925843

申请日：2010-10-29

申请人： Alexander Olek ,  Kurt Berlin

发明人： Alexander Olek ,  Kurt Berlin

IPC分类号： C12Q1/68

CPC分类号： C12Q1/686 ,  C12Q1/6816 ,  C12Q1/6827 ,  C12Q1/6837 ,  C12Q1/6872 ,  C12Q2523/125 ,  C12Q2565/519 ,  C12Q2565/627

摘要： Described is a method for detecting 5-methylcytosine in genomic DNA samples. First, a genomic DNA from a DNA sample is chemically converted with a reagent, 5-methylcytosine and cytosine reacting differently, and the pretreated DNA is subsequently amplified using a polymerase and at least one primer. In the next step, the amplified genomic DNA is hybridized to at least one oligonucleotide, forming a duplex, and said oligonucleotide is elongated by at least one nucleotide, the nucleotide carrying a detectable label, and the elongation depending on the methylation status of the specific cytosine in the genomic DNA sample. In the next step, the elongated oligonucleotides are analyzed for the presence of the label.

摘要翻译： 描述了在基因组DNA样品中检测5-甲基胞嘧啶的方法。 首先，DNA样品的基因组DNA用试剂化学转化，5-甲基胞嘧啶和胞嘧啶的反应不同，然后使用聚合酶和至少一种引物扩增预处理的DNA。 在下一步骤中，将扩增的基因组DNA与至少一种形成双链体的寡核苷酸杂交，并且所述寡核苷酸由至少一个核苷酸延伸，所述核苷酸携带可检测标记，延伸取决于具体的甲基化状态 基因组DNA样品中的胞嘧啶。 在下一步骤中，分析细长寡核苷酸的标记物的存在。

公开(公告)号：US07867701B2

公开(公告)日：2011-01-11

申请号：US10451646

申请日：2001-12-22

申请人： Jürgen Distler ,  Kurt Berlin ,  Alexander Olek

发明人： Jürgen Distler ,  Kurt Berlin ,  Alexander Olek

IPC分类号： C12Q1/68 ,  C12P19/34 ,  C07H21/04

CPC分类号： C12Q1/686 ,  C12Q2537/143 ,  C12Q2525/155

摘要： A method is described for the amplification of nucleic acids, in which the segments to be amplified are first hybridized with at least two primer oligonucleotides that have two domains, wherein the sequence-specific domain found at the 3-end hybridizes to the segment to be amplified, while the generic domain found at the 5-end does not hybridize. Then an amplification reaction is conducted by means of a polymerase and subsequently a labeled primer oligonucleotide, which binds to the generic domain of the first primer, is hybridized to the amplificate which is formed. In the last step, the sequence of the amplificate is investigated.

摘要翻译： 描述了用于扩增核酸的方法，其中待扩增的区段首先与具有两个结构域的至少两个引物寡核苷酸杂交，其中在3端发现的序列特异性结构域与所述区段杂交为 而5端发现的通用域不杂交。 然后通过聚合酶进行扩增反应，随后与第一引物的通用结构域结合的标记的引物寡核苷酸与所形成的扩增子杂交。 在最后一步中，调查扩增序列。

公开(公告)号：US07229759B2

公开(公告)日：2007-06-12

申请号：US10229370

申请日：2002-08-27

申请人： Alexander Olek ,  Kurt Berlin

发明人： Alexander Olek ,  Kurt Berlin

IPC分类号： C12Q1/68 ,  C12N15/11

CPC分类号： C12Q1/6827 ,  C12Q2523/125 ,  C12Q2537/163

摘要： The present invention concerns a method for the detection of cytosine methylation in DNA samples, wherein the following steps are conducted: (a) a genomic DNA sample, which comprises the DNA to be investigated and background DNA, is chemically treated in such a way that all of the unmethylated cytosine bases are converted to uracil, whereas the 5-methylcytosine bases remain unchanged; (b) the chemically treated DNA sample is amplified with the use of at least 1 primer oligonucleotide as well as a polymerase, whereby the DNA to be investigated is preferred as the template over the background DNA, and (c) the amplified products are analyzed and the methylation status in the DNA to be investigated is concluded from the presence of an amplified product and/or from the analysis of additional positions.

摘要翻译： 本发明涉及检测DNA样品中胞嘧啶甲基化的方法，其中进行以下步骤：（a）将包含待研究的DNA和背景DNA的基因组DNA样品进行化学处理，使其 所有未甲基化的胞嘧啶碱基被转化成尿嘧啶，而5-甲基胞嘧啶碱基保持不变; （b）使用至少1种引物寡核苷酸和聚合酶扩增化学处理的DNA样品，由此优选待研究的DNA作为背景DNA上的模板，（c）分析扩增产物 并且待研究的DNA中的甲基化状态从扩增产物的存在和/或从额外位置的分析得出。

公开(公告)号：US20130190205A1

公开(公告)日：2013-07-25

申请号：US13773480

申请日：2013-02-21

申请人： Alexander Olek ,  Kurt Berlin

发明人： Alexander Olek ,  Kurt Berlin

IPC分类号： C12Q1/68

CPC分类号： C12Q1/686 ,  C12Q1/6816 ,  C12Q1/6827 ,  C12Q1/6837 ,  C12Q1/6872 ,  C12Q2523/125 ,  C12Q2565/519 ,  C12Q2565/627

摘要： Described is a method for detecting 5-methylcytosine in genomic DNA samples. First, a genomic DNA from a DNA sample is chemically converted with a reagent, 5-methylcytosine and cytosine reacting differently, and the pretreated DNA is subsequently amplified using a polymerase and at least one primer. In the next step, the amplified genomic DNA is hybridized to at least one oligonucleotide, forming a duplex, and said oligonucleotide is elongated by at least one nucleotide, the nucleotide carrying a detectable label, and the elongation depending on the methylation status of the specific cytosine in the genomic DNA sample. In the next step, the elongated oligonucleotides are analyzed for the presence of the label.

摘要翻译： 描述了在基因组DNA样品中检测5-甲基胞嘧啶的方法。 首先，DNA样品的基因组DNA用试剂化学转化，5-甲基胞嘧啶和胞嘧啶的反应不同，然后使用聚合酶和至少一种引物扩增预处理的DNA。 在下一步骤中，将扩增的基因组DNA与至少一种形成双链体的寡核苷酸杂交，并且所述寡核苷酸由至少一个核苷酸延伸，所述核苷酸携带可检测标记，延伸取决于具体的甲基化状态 基因组DNA样品中的胞嘧啶。 在下一步骤中，分析细长寡核苷酸的标记物的存在。

公开(公告)号：US20070026393A1

公开(公告)日：2007-02-01

申请号：US10240970

申请日：2001-04-06

申请人： Kurt Berlin ,  Christian Piepenbrock ,  Alexander Olek

发明人： Kurt Berlin ,  Christian Piepenbrock ,  Alexander Olek

IPC分类号： C12Q1/68 ,  C07H21/04

CPC分类号： C07K14/82 ,  C07K14/4703 ,  C12Q1/6883 ,  C12Q2600/154

摘要： The invention describes a set of oligonucleotides as probes for the detection of relevant variations of DNA methylation in a target group of genes, the use thereof for the detection of gene variants with respect to DNA methylation, a medical device which uses a set of oligonucleotides, a method for investigating the methylation state of an individual as well as a method for creating a model for evaluating the probability of occurrence of a health problem of an individual. Such disorders can be: undesired drug interactions cancer diseases CNS malfunctions, damage or disease symptoms of aggression or behavioral disturbances clinical, psychological and social consequences of brain lesions psychotic disturbances and personality disorders dementia and/or associated syndromes cardiovascular disorder, malfunction and damage malfunction, damage or disorder of the gastrointestinal tract malfunction, damage or disorder of the respiratory system lesion, inflammation, infection, immunity and/or convalescence malfunction, damage or disease of the body as an abnormality in the development process malfunction, damage or disorder of the skin, the muscles, the connective tissue or the bones endocrine and metabolic malfunction, damage or disorder headaches or sexual malfunction.

摘要翻译： 本发明描述了一组寡核苷酸作为用于检测靶基因组中DNA甲基化的相关变异的探针，其用于检测关于DNA甲基化的基因变体的用途，使用一组寡核苷酸的医疗装置， 用于研究个体的甲基化状态的方法以及用于创建用于评估个体的健康问题的发生概率的模型的方法。 这种疾病可以是：不期望的药物相互作用癌症疾病中枢神经系统疾病，侵袭或行为障碍的损伤或疾病症状临床，脑损伤的心理和社会后果精神障碍和人格障碍痴呆和/或相关综合征心血管疾病，故障和损伤故障， 胃肠道的损伤或紊乱，呼吸系统病变的损伤或紊乱，炎症，感染，免疫和/或康复失败，身体的损伤或疾病，作为发育过程失败的异常，皮肤的损伤或障碍 ，肌肉，结缔组织或骨骼内分泌和代谢功能障碍，损伤或障碍性头痛或性功能障碍。

公开(公告)号：US20060136142A1

公开(公告)日：2006-06-22

申请号：US10774052

申请日：2004-02-06

申请人： Kurt Berlin ,  Alexander Olek ,  Christian Piepenbrock

发明人： Kurt Berlin ,  Alexander Olek ,  Christian Piepenbrock

IPC分类号： G06F19/00

CPC分类号： G06Q50/24 ,  G16B20/00 ,  Y02A90/22 ,  Y02A90/26

摘要： Systems, methods and computer program products for guiding selection of a therapeutic treatment regimen or a preventive therapeutic treatment regimen are disclosed. The method comprises (A) providing to a computing device comprising a first knowledge base comprising information about a plurality of different methylation statuses at selected sites of the DNA in cells with a known disease or medical condition and/or healthy cells, a second knowledge base comprising a plurality of expert rules for evaluating and selecting a type of disease or medical condition based on the methylation status at selected sites of the DNA of a patient, (B) generating in said computing device a ranked listing of diseases or medical conditions based on the information about the methylation status at selected sites of the DNA of the patient, the first knowledge base and the second knowledge base.

摘要翻译： 公开了用于指导选择治疗方案或预防性治疗方案的系统，方法和计算机程序产品。 该方法包括（A）提供给包括第一知识库的计算设备，所述第一知识库包括关于具有已知疾病或医学状况和/或健康细胞的细胞中所述DNA的选定位点处的多个不同甲基化状态的信息，和第二知​​识库 包括用于基于患者的DNA的选定位点处的甲基化状态来评估和选择疾病或医学状况的多种专家规则，（B）在所述计算设备中产生基于以下的疾病或医疗状况的排名列表： 关于患者DNA选定位点甲基化状态的信息，第一知识库和第二知识库。

公开(公告)号：US07824852B2

公开(公告)日：2010-11-02

申请号：US10220896

申请日：2001-02-23

申请人： Alexander Olek ,  Kurt Berlin

发明人： Alexander Olek ,  Kurt Berlin

IPC分类号： C07H21/04 ,  C12Q1/68

CPC分类号： C12Q1/686 ,  C12Q1/6816 ,  C12Q1/6827 ,  C12Q1/6837 ,  C12Q1/6872 ,  C12Q2523/125 ,  C12Q2565/519 ,  C12Q2565/627

摘要： Described is a method for detecting 5-methylcytosine in genomic DNA samples. First, a genomic DNA from a DNA sample is chemically converted with a reagent, 5-methylcytosine and cytosine reacting differently, and the pretreated DNA is subsequently amplified using a polymerase and at least one primer. In the next step, the amplified genomic DNA is hybridized to at least one oligonucleotide, forming a duplex, and said oligonucleotide is elongated by at least one nucleotide, the nucleotide carrying a detectable label, and the elongation depending on the methylation status of the specific cytosine in the genomic DNA sample. In the next step, the elongated oligonucleotides are analyzed for the presence of the label.

摘要翻译： 描述了在基因组DNA样品中检测5-甲基胞嘧啶的方法。 首先，DNA样品的基因组DNA用试剂化学转化，5-甲基胞嘧啶和胞嘧啶的反应不同，然后使用聚合酶和至少一种引物扩增预处理的DNA。 在下一步骤中，将扩增的基因组DNA与至少一种形成双链体的寡核苷酸杂交，并且所述寡核苷酸由至少一个核苷酸延伸，所述核苷酸携带可检测标记，延伸取决于具体的甲基化状态 基因组DNA样品中的胞嘧啶。 在下一步骤中，分析细长寡核苷酸的标记物的存在。