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1. 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.

2. 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。

3. 发明申请

US20120122701A1 Methods for Non-Invasive Prenatal Paternity Testing 审中-公开
标题翻译：非侵入性产前亲子鉴定方法
公开(公告)号：US20120122701A1
公开(公告)日：2012-05-17
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： C12Q1/68 , G01N33/53 , G01N21/64 , C40B20/00
CPC分类号： C12Q1/6869 , C12Q1/6876 , C12Q2600/156 , 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.
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。

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

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.

6. 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。

7. 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.

8. 发明申请

US20120185176A1 Methods for Non-Invasive Prenatal Ploidy Calling 审中-公开
标题翻译：非侵入性产前倍性调用方法
公开(公告)号：US20120185176A1
公开(公告)日：2012-07-19
申请号：US13499086
申请日：2010-09-30
申请人： Matthew Rabinowitz , Allison Ryan , George Gemelos , Milena Banjevic , Zachary Demko
发明人： Matthew Rabinowitz , Allison Ryan , George Gemelos , Milena Banjevic , Zachary Demko
IPC分类号： G06F19/00
CPC分类号： G16B30/00 , C12Q1/6827 , C12Q1/6874 , C12Q1/6876 , C12Q1/6883 , C12Q2600/156 , C12Q2600/16 , G06N7/005 , G16B20/00 , C12Q2537/16 , C12Q2537/165
摘要： Disclosed herein are methods for determining the copy number of a chromosome in a fetus in the context of non-invasive prenatal diagnosis. In an embodiment, the measured genetic data from a sample of genetic material that contains both fetal DNA and maternal DNA is analyzed, along with the genetic data from the biological parents of the fetus, and the copy number of the chromosome of interest is determined. In an embodiment, the maternal serum is measured using a single-nucleotide polymorphism (SNP) microarray, along with parental genomic data, and the determination of the chromosome copy number is used to make clinical decisions pertaining to the fetus.
摘要翻译：本文公开了用于在非侵入性产前诊断的上下文中确定胎儿中染色体的拷贝数的方法。在一个实施方案中，分析来自含有胎儿DNA和母体DNA的遗传物质的样品的测量的遗传数据以及来自胎儿的生物亲本的遗传数据，并确定感兴趣的染色体的拷贝数。在一个实施方案中，使用单核苷酸多态性（SNP）微阵列以及亲本基因组数据测量母体血清，并且使用染色体拷贝数的确定来进行与胎儿有关的临床决定。

9. 发明申请

US20130274116A1 METHODS FOR NON-INVASIVE PRENATAL PLOIDY CALLING 审中-公开
标题翻译：非侵入式预防性呼吸方法
公开(公告)号：US20130274116A1
公开(公告)日：2013-10-17
申请号：US13896293
申请日：2013-05-16
申请人： Matthew Rabinowitz , Allison Rayan , George Gemelos , Milena Banjevic , Zachary Demko
发明人： Matthew Rabinowitz , Allison Rayan , George Gemelos , Milena Banjevic , Zachary Demko
IPC分类号： C12Q1/68
CPC分类号： G16B30/00 , C12Q1/6827 , C12Q1/6874 , C12Q1/6876 , C12Q1/6883 , C12Q2600/156 , C12Q2600/16 , G06N7/005 , G16B20/00 , C12Q2537/16 , C12Q2537/165
摘要： Disclosed herein are methods for determining the copy number of a chromosome in a fetus in the context of non-invasive prenatal diagnosis. In an embodiment, the measured genetic data from a sample of genetic material that contains both fetal DNA and maternal DNA is analyzed, along with the genetic data from the biological parents of the fetus, and the copy number of the chromosome of interest is determined. In an embodiment, the maternal serum is measured using a single-nucleotide polymorphism (SNP) microarray, along with parental genomic data, and the determination of the chromosome copy number is used to make clinical decisions pertaining to the fetus.
摘要翻译：本文公开了用于在非侵入性产前诊断的上下文中确定胎儿中染色体的拷贝数的方法。在一个实施方案中，分析来自含有胎儿DNA和母体DNA的遗传物质的样品的测量的遗传数据以及来自胎儿的生物亲本的遗传数据，并确定感兴趣的染色体的拷贝数。在一个实施方案中，使用单核苷酸多态性（SNP）微阵列以及亲本基因组数据测量母体血清，并且使用染色体拷贝数的确定来进行与胎儿有关的临床决定。

10. 发明申请

US20130252824A1 SYSTEM AND METHOD FOR CLEANING NOISY GENETIC DATA FROM TARGET INDIVIDUALS USING GENETIC DATA FROM GENETICALLY RELATED INDIVIDUALS 有权
标题翻译：使用遗传资料从遗传相关个体清除目标个体的噪声遗传数据的系统和方法
公开(公告)号：US20130252824A1
公开(公告)日：2013-09-26
申请号：US13793186
申请日：2013-03-11
申请人： Matthew Rabinowitz , Milena Banjevic , Zachary Demko , David Johnson
发明人： Matthew Rabinowitz , Milena Banjevic , Zachary Demko , David Johnson
IPC分类号： G06F19/20
CPC分类号： G06F19/20 , G06F19/18
摘要： A system and method for determining the genetic data for one or a small set of cells, or from fragmentary DNA, where a limited quantity of genetic data is available, are disclosed. Genetic data for the target individual is acquired and amplified using known methods, and poorly measured base pairs, missing alleles and missing regions are reconstructed using expected similarities between the target genome and the genome of genetically related subjects. In accordance with one embodiment of the invention, incomplete genetic data is acquired from embryonic cells, fetal cells, or cell-free fetal DNA isolated from the mother's blood, and the incomplete genetic data is reconstructed using the more complete genetic data from a larger sample diploid cells from one or both parents, with or without genetic data from haploid cells from one or both parents, and/or genetic data taken from other related individuals.
摘要翻译：公开了一种用于确定一个或一小组细胞遗传数据的系统和方法，或从有限数量的遗传数据获得的片段DNA。使用已知方法获取和扩增目标个体的遗传数据，并且使用目标基因组与基因相关受试者的基因组之间的预期相似性重建差测量的碱基对，缺失的等位基因和缺失区域。根据本发明的一个实施方案，从母体血液中分离的胚胎细胞，胎儿细胞或无细胞胎儿DNA获得不完整的遗传数据，并且使用更大的样本的更完整的遗传数据来重建不完整的遗传数据来自一个或两个父母的二倍体细胞，具有或不具有来自一个或两个亲本的单倍体细胞的遗传数据和/或从其他相关个体获取的遗传数据。

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