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1. 发明申请

US20110033862A1 METHODS FOR CELL GENOTYPING 审中-公开
标题翻译：细胞基因分析方法
公开(公告)号：US20110033862A1
公开(公告)日：2011-02-10
申请号：US12918445
申请日：2009-02-19
申请人： Matthew Rabinowitz , David S. Johnson , Johan Baner , Zachary Demko , Cengiz Cinnioglu
发明人： Matthew Rabinowitz , David S. Johnson , Johan Baner , Zachary Demko , Cengiz Cinnioglu
IPC分类号： C12Q1/68 , C12P19/34
CPC分类号： C12Q1/6876 , C12Q2600/156 , C12Q2600/16 , C12Q2600/172
摘要： Methods for cell genotyping are disclosed herein. A method for determining the genomic data of one or a small number of cells, or from fragmentary DNA, where a limited quantity of genetic data is available may include adding one or more targeted primers to a whole genome amplification of a cell, increasing the accuracy with which key alleles are measured in the context of a whole genome amplification. The genetic material from a single cell may be divided into fractions, each of which may be separately genotyped, allowing the reconstruction of the cells haplotype. The genetic material from a single cell may be divided into fractions, each of which may be separately genotyped, and the distribution of the various alleles in the different fractions may be used to determine the ploidy state of one or a plurality of chromosomes in the cell.
摘要翻译：本文公开了细胞基因分型的方法。用于确定有限数量的遗传数据可用的一个或少数细胞或来自片段DNA的基因组数据的方法可包括向细胞的全基因组扩增添加一种或多种靶向引物，增加细胞的准确度在全基因组扩增的情况下测量关键等位基因。来自单个细胞的遗传物质可以被分成各自的部分，每一个可以分开进行基因分型，允许重建细胞单元型。来自单个细胞的遗传物质可以分成各自的部分，每个可以分别进行基因分型，并且可以使用不同级分中各种等位基因的分布来确定细胞中一条或多条染色体的倍性状态。

2. 发明授权

US10017812B2 Methods for non-invasive prenatal ploidy calling 有权
公开(公告)号：US10017812B2
公开(公告)日：2018-07-10
申请号：US13300235
申请日：2011-11-18
申请人： Matthew Rabinowitz , George Gemelos , Milena Banjevic , Allison Ryan , Zachary Demko , Matthew Hill , Bernhard Zimmermann , Johan Baner
发明人： Matthew Rabinowitz , George Gemelos , Milena Banjevic , Allison Ryan , Zachary Demko , Matthew Hill , Bernhard Zimmermann , Johan Baner
IPC分类号： G01N33/48 , G01N31/00 , G06G7/48 , G06G7/58 , C12Q1/6869 , C12Q1/6827 , G06F19/18 , C12Q1/6883 , C12Q1/6862 , G06F19/24
CPC分类号： C12Q1/6869 , C12Q1/6806 , C12Q1/6827 , C12Q1/686 , C12Q1/6862 , C12Q1/6874 , C12Q1/6883 , C12Q2600/156 , C12Q2600/16 , G06F19/34 , G16B20/00 , G16B40/00 , C12Q2537/161 , C12Q2537/165 , C12Q2537/143
摘要： The present disclosure provides methods for determining the ploidy status of a chromosome in a gestating fetus from genotypic data measured from a mixed sample of DNA comprising DNA from both the mother of the fetus and from the fetus, and optionally from genotypic data from the mother and father. The ploidy state is determined by using a joint distribution model to create a plurality of expected allele distributions for different possible fetal ploidy states given the parental genotypic data, and comparing the expected allelic distributions to the pattern of measured allelic distributions measured in the mixed sample, and choosing the ploidy state whose expected allelic distribution pattern most closely matches the observed allelic distribution pattern. The mixed sample of DNA may be preferentially enriched at a plurality of polymorphic loci in a way that minimizes the allelic bias, for example using massively multiplexed targeted PCR.

3. 发明申请

US20140065621A1 METHODS FOR INCREASING FETAL FRACTION IN MATERNAL BLOOD 审中-公开
标题翻译：用于增加母体中的胎儿分数的方法
公开(公告)号：US20140065621A1
公开(公告)日：2014-03-06
申请号：US13793316
申请日：2013-03-11
申请人： Ravi Mhatre , Johan Baner , Bernhard Zimmermann , Matthew Hill , Zachary Demko
发明人： Ravi Mhatre , Johan Baner , Bernhard Zimmermann , Matthew Hill , Zachary Demko
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6883 , A23D9/00 , C12Q2600/118 , C12Q2600/156
摘要： The invention provides methods of increasing the fetal fraction in maternal blood and plasma. This increase in fetal fraction improves the accuracy and decreases the “no call” rate for prenatal testing that measures fetal DNA in maternal blood.
摘要翻译：本发明提供了增加母体血液和血浆中胎儿分数的方法。胎儿分数的这种增加提高了准确性，降低了测量母体血液胎儿DNA的产前测试的“无呼叫”率。

4. 发明申请

US20110288780A1 Methods for Non-Invasive Prenatal Ploidy Calling 有权
标题翻译：非侵入性产前倍性调用方法
公开(公告)号：US20110288780A1
公开(公告)日：2011-11-24
申请号：US13110685
申请日：2011-05-18
申请人： Matthew Rabinowitz , George Gemelos , Milena Banjevic , Allison Ryan , Zachary Demko , Matthew Hill , Bernhard Zimmermann , Johan Baner
发明人： Matthew Rabinowitz , George Gemelos , Milena Banjevic , Allison Ryan , Zachary Demko , Matthew Hill , Bernhard Zimmermann , Johan Baner
IPC分类号： G06F19/00 , C07H21/04
CPC分类号： C12Q1/6883 , C12Q1/6827 , C12Q1/6869 , C12Q2537/161 , C12Q2537/165 , C12Q2600/112 , C12Q2600/156 , C12Q2600/16 , C12Q2600/172 , G06F19/00 , G06F19/12 , G06F19/18 , G06F19/22 , G06F19/34 , G16H50/30
摘要： Methods for non-invasive prenatal ploidy calling are disclosed herein. Methods for determining the ploidy status of a chromosome in a gestating fetus from genotypic data measured from a sample of DNA from the mother of the fetus and from the fetus, and from genotypic data from the mother and optionally also from the father are disclosed herein. The ploidy state is determined by using a joint distribution model to create a set of expected allele distributions for different possible fetal ploidy states given the parental genotypic data, and comparing the expected allelic distributions to the pattern of measured allelic distributions measured in the mixed sample, and choosing the ploidy state whose expected allelic distribution pattern most closely matches the observed allelic distribution pattern. In an embodiment, the mixed sample of DNA may be preferentially enriched at a plurality of polymorphic loci in a way that minimizes the allelic bias.
摘要翻译：本文公开了非侵入性产前倍性呼叫的方法。本文公开了从胎儿母体和胎儿的DNA样本以及来自母亲和任选也来自父亲的基因型数据测量的基因型数据中确定妊娠胎儿染色体倍性状态的方法。通过使用联合分布模型来确定给定父母基因型数据的不同可能胎儿倍性状态的一组预期等位基因分布，并将预期等位基因分布与在混合样品中测量的测量等位基因分布的模式进行比较来确定倍性状态，并选择其预期等位基因分布模式与观察到的等位基因分布模式最接近的倍性状态。在一个实施方案中，DNA的混合样品可以以使等位基因偏倚最小化的方式优先富集在多个多态位点。

5. 发明授权

US08825412B2 Methods for non-invasive prenatal ploidy calling 有权
标题翻译：非侵入性产前倍性调用方法
公开(公告)号：US08825412B2
公开(公告)日：2014-09-02
申请号：US13110685
申请日：2011-05-18
申请人： Matthew Rabinowitz , George Gemelos , Milena Banjevic , Allison Ryan , Zachary Demko , Matthew Hill , Bernhard Zimmermann , Johan Baner
发明人： Matthew Rabinowitz , George Gemelos , Milena Banjevic , Allison Ryan , Zachary Demko , Matthew Hill , Bernhard Zimmermann , Johan Baner
IPC分类号： G01N33/48 , G06F19/00 , G01N31/00 , G06G7/48 , G06G7/58 , G06F19/12 , C12Q1/68
CPC分类号： C12Q1/6883 , C12Q1/6827 , C12Q1/6869 , C12Q2537/161 , C12Q2537/165 , C12Q2600/112 , C12Q2600/156 , C12Q2600/16 , C12Q2600/172 , G06F19/00 , G06F19/12 , G06F19/18 , G06F19/22 , G06F19/34 , G16H50/30
摘要： Methods for non-invasive prenatal ploidy calling are disclosed herein. Methods for determining the ploidy status of a chromosome in a gestating fetus from genotypic data measured from a sample of DNA from the mother of the fetus and from the fetus, and from genotypic data from the mother and optionally also from the father are disclosed herein. The ploidy state is determined by using a joint distribution model to create a set of expected allele distributions for different possible fetal ploidy states given the parental genotypic data, and comparing the expected allelic distributions to the pattern of measured allelic distributions measured in the mixed sample, and choosing the ploidy state whose expected allelic distribution pattern most closely matches the observed allelic distribution pattern. In an embodiment, the mixed sample of DNA may be preferentially enriched at a plurality of polymorphic loci in a way that minimizes the allelic bias.
摘要翻译：本文公开了非侵入性产前倍性呼叫的方法。本文公开了从胎儿母体和胎儿的DNA样本以及来自母亲和任选也来自父亲的基因型数据测量的基因型数据中确定妊娠胎儿染色体倍性状态的方法。通过使用联合分布模型来确定给定父母基因型数据的不同可能胎儿倍性状态的一组预期等位基因分布，并将预期等位基因分布与在混合样品中测量的测量等位基因分布的模式进行比较来确定倍性状态，并选择其预期等位基因分布模式与观察到的等位基因分布模式最接近的倍性状态。在一个实施方案中，DNA的混合样品可以以使等位基因偏倚最小化的方式优先富集在多个多态位点。

6. 发明申请

US20120270212A1 Methods for Non-Invasive Prenatal Ploidy Calling 有权
标题翻译：非侵入性产前倍性调用方法
公开(公告)号：US20120270212A1
公开(公告)日：2012-10-25
申请号：US13300235
申请日：2011-11-18
申请人： MATTHEW RABINOWITZ , GEORGE GEMELOS , MILENA BANJEVIC , ALLISON RYAN , ZACHARY DEMKO , MATTHEW HILL , BERNHARD ZIMMERMANN , JOHAN BANER
发明人： MATTHEW RABINOWITZ , GEORGE GEMELOS , MILENA BANJEVIC , ALLISON RYAN , ZACHARY DEMKO , MATTHEW HILL , BERNHARD ZIMMERMANN , JOHAN BANER
IPC分类号： C12Q1/68 , G06F19/20 , G06F19/24
CPC分类号： C12Q1/6869 , C12Q1/6806 , C12Q1/6827 , C12Q1/6862 , C12Q1/6874 , C12Q1/6883 , C12Q2600/156 , G06F19/18 , G06F19/24 , C12Q2537/161 , C12Q2537/165
摘要： The present disclosure provides methods for determining the ploidy status of a chromosome in a gestating fetus from genotypic data measured from a mixed sample of DNA comprising DNA from both the mother of the fetus and from the fetus, and optionally from genotypic data from the mother and father. The ploidy state is determined by using a joint distribution model to create a plurality of expected allele distributions for different possible fetal ploidy states given the parental genotypic data, and comparing the expected allelic distributions to the pattern of measured allelic distributions measured in the mixed sample, and choosing the ploidy state whose expected allelic distribution pattern most closely matches the observed allelic distribution pattern. The mixed sample of DNA may be preferentially enriched at a plurality of polymorphic loci in a way that minimizes the allelic bias, for example using massively multiplexed targeted PCR.
摘要翻译：本公开提供了从包括来自胎儿母体和胎儿的DNA的DNA的混合样品测量的基因型数据以及任选地来自母体的基因型数据以及任选地从胎儿的基因型数据确定胎儿胎儿的染色体的倍性状态的方法父亲。通过使用联合分布模型来确定给定父母基因型数据的不同可能胎儿倍性状态的多个预期等位基因分布，并将预期等位基因分布与混合样品中测量的等位基因分布的模式进行比较来确定倍性状态，并选择其预期等位基因分布模式与观察到的等位基因分布模式最接近的倍性状态。 DNA的混合样品可以以使等位基因偏倚最小化的方式优先富集在多个多态性位点，例如使用大规模复用的靶向PCR。

7. 发明授权

US10113196B2 Prenatal paternity testing using maternal blood, free floating fetal DNA and SNP genotyping 有权
公开(公告)号：US10113196B2
公开(公告)日：2018-10-30
申请号：US13335043
申请日：2011-12-22
申请人： Allison Ryan , Styrmir Sigurjonsson , Milena Banjevic , George Gemelos , Matthew Hill , Johan Baner , Matthew Rabinowitz , Zachary Demko
发明人： Allison Ryan , Styrmir Sigurjonsson , Milena Banjevic , George Gemelos , Matthew Hill , Johan Baner , Matthew Rabinowitz , Zachary Demko
IPC分类号： C12Q1/6869 , C12Q1/6876 , G06F19/14
摘要： Methods for non-invasive prenatal paternity testing are disclosed herein. The method uses genetic measurements made on plasma taken from a pregnant mother, along with genetic measurements of the alleged father, and genetic measurements of the mother, to determine whether or not the alleged father is the biological father of the fetus. This is accomplished by way of an informatics based method that can compare the genetic fingerprint of the fetal DNA found in maternal plasma to the genetic fingerprint of the alleged father.

8. 发明申请

US20150232938A1 METHODS FOR INCREASING FETAL FRACTION IN MATERNAL BLOOD 审中-公开
标题翻译：用于增加母体中的胎儿分数的方法
公开(公告)号：US20150232938A1
公开(公告)日：2015-08-20
申请号：US14704314
申请日：2015-05-05
申请人： Ravi Mhatre , Johan Baner , Bernhard Zimmermann , Matthew Micah Hill , Zachary Demko
发明人： Ravi Mhatre , Johan Baner , Bernhard Zimmermann , Matthew Micah Hill , Zachary Demko
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6883 , A23D9/00 , C12Q2600/118 , C12Q2600/156
摘要： The invention provides methods of increasing the fetal fraction in maternal blood and plasma. This increase in fetal fraction improves the accuracy and decreases the “no call” rate for prenatal testing that measures fetal DNA in maternal blood.
摘要翻译：本发明提供了增加母体血液和血浆中胎儿分数的方法。胎儿分数的这种增加提高了准确性，降低了测量母体血液胎儿DNA的产前测试的“无呼叫”率。

9. 发明申请

US20130261004A1 METHODS FOR NON-INVASIVE PRENATAL PATERNITY TESTING 审中-公开
标题翻译：非侵入性预防性试验方法
公开(公告)号：US20130261004A1
公开(公告)日：2013-10-03
申请号：US13846160
申请日：2013-03-18
申请人： Allison Ryan , Styrmir Sigurjonsson , Milena Banjevic , George Gemelos , Matthew Hill , Johan Baner , Matthew Rabinowitz , Zachary Demko
发明人： Allison Ryan , Styrmir Sigurjonsson , Milena Banjevic , George Gemelos , Matthew Hill , Johan Baner , Matthew Rabinowitz , Zachary Demko
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6869 , C12Q1/6876 , C12Q2600/156 , G16B10/00
摘要： Methods for non-invasive prenatal paternity testing are disclosed herein. The method uses genetic measurements made on plasma taken from a pregnant mother, along with genetic measurements of the alleged father, and genetic measurements of the mother, to determine whether or not the alleged father is the biological father of the fetus. This is accomplished by way of an informatics based method that can compare the genetic fingerprint of the fetal DNA found in maternal plasma to the genetic fingerprint of the alleged father.
摘要翻译：本文公开了非侵入性产前亲子鉴定的方法。该方法使用从怀孕母亲获得的血浆进行的遗传测量，以及所称父亲的遗传测量以及母亲的遗传测量，以确定所称父亲是否是胎儿的生物之父。这通过基于信息学的方法来实现，该方法可以将母体血浆中发现的胎儿DNA的遗传指纹与所称父亲的遗传指纹进行比较。

10. 发明申请

US20130178373A1 METHODS FOR NON-INVASIVE PRENATAL PLOIDY CALLING 有权
公开(公告)号：US20130178373A1
公开(公告)日：2013-07-11
申请号：US13791397
申请日：2013-03-08
申请人： Matthew Rabinowitz , George Gemelos , Milena Banjevic , Allison Ryan , Zachary Demko , Matthew Hill , Bernhard Zimmermann , Johan Baner
发明人： Matthew Rabinowitz , George Gemelos , Milena Banjevic , Allison Ryan , Zachary Demko , Matthew Hill , Bernhard Zimmermann , Johan Baner
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6869 , C12Q1/6806 , C12Q1/6827 , C12Q1/6862 , C12Q1/6874 , C12Q1/6883 , C12Q2600/156 , G06F19/18 , G06F19/24 , C12Q2537/161 , C12Q2537/165
摘要： The present disclosure provides methods for determining the ploidy status of a chromosome in a gestating fetus from genotypic data measured from a mixed sample of DNA comprising DNA from both the mother of the fetus and from the fetus, and optionally from genotypic data from the mother and father. The ploidy state is determined by using a joint distribution model to create a plurality of expected allele distributions for different possible fetal ploidy states given the parental genotypic data, and comparing the expected allelic distributions to the pattern of measured allelic distributions measured in the mixed sample, and choosing the ploidy state whose expected allelic distribution pattern most closely matches the observed allelic distribution pattern. The mixed sample of DNA may be preferentially enriched at a plurality of polymorphic loci in a way that minimizes the allelic bias, for example using massively multiplexed targeted PCR.

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