公开(公告)号：EP2854057B1

公开(公告)日：2018-03-07

申请号：EP14198470.8

申请日：2011-05-18

申请人： Natera, Inc.

发明人： Rabinowitz, Matthew ,  Gemelos, George ,  Banjevic, Milena ,  Ryan, Allison ,  Demko, Zachary ,  Hill, Matthew ,  Zimmermann, Bernhard ,  Baner, Johan

IPC分类号： G06F19/18 ,  G06F19/22 ,  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.

公开(公告)号：EP2854058A2

公开(公告)日：2015-04-01

申请号：EP14198478.1

申请日：2011-05-18

申请人： Natera, Inc.

发明人： Rabinowitz, Matthew ,  Gemelos, George ,  Banjevic, Milena ,  Ryan, Allison ,  Demko, Zachary ,  Hill, Matthew ,  Zimmermann, Bernhard ,  Baner, Johan

IPC分类号： G06F19/18 ,  G06F19/22 ,  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调用的方法。 本文公开了根据从胎儿和胎儿的DNA样品测量的基因型数据以及从母亲和可选地来自父亲的基因型数据测定妊娠胎儿中染色体倍性状态的方法。 通过使用联合分布模型来确定倍性状态，以在给定亲本基因型数据的情况下针对不同可能的胎儿倍性状态创建一组预期的等位基因分布，并且将预期的等位基因分布与在混合样品中测量的测量的等位基因分布的模式进行比较， 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匹配的倍性状态。 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在多个多态性基因座上优先富集。

公开(公告)号：EP2854058A3

公开(公告)日：2015-10-28

申请号：EP14198478.1

申请日：2011-05-18

申请人： Natera, Inc.

发明人： Rabinowitz, Matthew ,  Gemelos, George ,  Banjevic, Milena ,  Ryan, Allison ,  Demko, Zachary ,  Hill, Matthew ,  Zimmermann, Bernhard ,  Baner, Johan

IPC分类号： G06F19/18 ,  G06F19/22 ,  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.

公开(公告)号：EP2854057A3

公开(公告)日：2015-08-26

申请号：EP14198470.8

申请日：2011-05-18

申请人： Natera, Inc.

发明人： Rabinowitz, Matthew ,  Gemelos, George ,  Banjevic, Milena ,  Ryan, Allison ,  Demko, Zachary ,  Hill, Matthew ,  Zimmermann, Bernhard ,  Baner, Johan

IPC分类号： G06F19/18 ,  G06F19/22 ,  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.

公开(公告)号：EP2902500A1

公开(公告)日：2015-08-05

申请号：EP14195468.5

申请日：2011-11-18

申请人： Natera, Inc.

发明人： Rabinowitz, Matthew ,  Gemelos, George ,  BanjevicC, Milena ,  Ryan, Allison ,  Demko, Zachary ,  Hill, Matthew ,  Zimmerman, Bernhard ,  Baner, Johan

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6883 ,  C12Q1/6827 ,  C12Q1/686 ,  C12Q1/6869 ,  C12Q2600/156 ,  C12Q2600/16 ,  G06F19/00 ,  G06F19/18 ,  G06F19/34 ,  C12Q2537/161 ,  C12Q2537/165 ,  C12Q2527/113 ,  C12Q2527/143 ,  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.

摘要翻译： 本公开内容提供用于根据从包含来自胎儿母亲和来自胎儿的DNA的DNA混合样品测量的基因型数据和任选来自母亲的基因型数据测定妊娠胎儿中染色体倍性状态的方法，和 父亲。 通过使用联合分布模型来确定倍性状态，以在给定亲本基因型数据的情况下针对不同的可能的胎儿倍性状态产生多个预期的等位基因分布，并且将预期的等位基因分布与在混合样品中测量的测量的等位基因分布的模式进行比较， 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匹配的倍性状态。 可以以使等位基因偏倚最小化的方式，例如使用大规模多重靶向PCR，使DNA的混合样品优先在多个多态性基因座处富集。

公开(公告)号：EP2854057A2

公开(公告)日：2015-04-01

申请号：EP14198470.8

申请日：2011-05-18

申请人： Natera, Inc.

发明人： Rabinowitz, Matthew ,  Gemelos, George ,  Banjevic, Milena ,  Ryan, Allison ,  Demko, Zachary ,  Hill, Matthew ,  Zimmermann, Bernhard ,  Baner, Johan

IPC分类号： G06F19/18 ,  G06F19/22 ,  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来自胎儿的DNA的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胎儿胎儿的倍性状态的方法。 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的胎儿倍性状态的一组预期等位基因分布，并将预期的等位基因分布与在混合样品中测量的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为匹配的倍性状态。 在一个实施方案中，DNA的混合样品可以以最小化等位基因偏倚的方式优先富集在多个多态位点。

公开(公告)号：EP2902500B1

公开(公告)日：2017-01-11

申请号：EP14195468.5

申请日：2011-11-18

申请人： Natera, Inc.

发明人： Rabinowitz, Matthew ,  Gemelos, George ,  Banjevic, Milena ,  Ryan, Allison ,  Demko, Zachary ,  Hill, Matthew ,  Zimmermann, Bernhard ,  Baner, Johan

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6883 ,  C12Q1/6827 ,  C12Q1/686 ,  C12Q1/6869 ,  C12Q2600/156 ,  C12Q2600/16 ,  G06F19/00 ,  G06F19/18 ,  G06F19/34 ,  C12Q2537/161 ,  C12Q2537/165 ,  C12Q2527/113 ,  C12Q2527/143 ,  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.

摘要翻译： 本公开提供了从包括来自胎儿的母体和来自胎儿的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中确定妊娠胎儿中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的胎儿倍性状态的多个预期等位基因分布，并将预期的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为匹配的倍性状态。 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。

公开(公告)号：EP2854056A3

公开(公告)日：2015-06-03

申请号：EP14198110.0

申请日：2010-09-30

申请人： Natera, Inc.

发明人： Rabinowitz, Matthew ,  Ryan, Allison ,  Gemelos, George ,  Banjevic, Milena ,  Demko, Zachary

IPC分类号： G06F19/18 ,  C12Q1/68

CPC分类号： G06F19/22 ,  C12Q1/6827 ,  C12Q1/6874 ,  C12Q1/6876 ,  C12Q1/6883 ,  C12Q2600/156 ,  C12Q2600/16 ,  G06F19/18 ,  G06N7/005 ,  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背景下确定胎儿中染色体拷贝数的方法。 在一个实施方案中，分析来自含有胎儿DNA和母体DNA两者的遗传物质样品的测量基因数据以及来自胎儿生物学亲本的遗传数据，并确定感兴趣染色体的拷贝数。 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做出与胎儿有关的临床决定。

公开(公告)号：EP2854056A2

公开(公告)日：2015-04-01

申请号：EP14198110.0

申请日：2010-09-30

申请人： Natera, Inc.

发明人： Rabinowitz, Matthew ,  Ryan, Allison ,  Gemelos, George ,  Banjevic, Milena ,  Demko, Zachary

IPC分类号： G06F19/18 ,  C12Q1/68

CPC分类号： G06F19/22 ,  C12Q1/6827 ,  C12Q1/6874 ,  C12Q1/6876 ,  C12Q1/6883 ,  C12Q2600/156 ,  C12Q2600/16 ,  G06F19/18 ,  G06N7/005 ,  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.