公开(公告)号：US11345962B2

公开(公告)日：2022-05-31

申请号：US16796748

申请日：2020-02-20

申请人： Natera, Inc.

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

IPC分类号： C12Q1/6869 ,  G16B10/00 ,  C12Q1/6876 ,  C12Q1/6844

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.

公开(公告)号：US11111545B2

公开(公告)日：2021-09-07

申请号：US17061877

申请日：2020-10-02

申请人： Natera, Inc.

发明人： Joshua Babiarz ,  Tudor Pompiliu Constantin ,  Lane A. Eubank ,  George Gemelos ,  Matthew Micah Hill ,  Huseyin Eser Kirkizlar ,  Matthew Rabinowitz ,  Onur Sakarya ,  Styrmir Sigurjonsson ,  Bernhard Zimmermann ,  Johan Baner ,  Allison Ryan ,  Milena Banjevic ,  Zachary Demko

IPC分类号： C12Q1/68 ,  C12Q1/6883 ,  C12Q1/6811 ,  C12Q1/6848 ,  C12Q1/6851 ,  C12Q1/6855 ,  C12Q1/6874 ,  C12Q1/6809

摘要： The invention provides methods for simultaneously amplifying multiple nucleic acid regions of interest in one reaction volume as well as methods for selecting a library of primers for use in such amplification methods. The invention also provides library of primers with desirable characteristics, such as minimal formation of amplified primer dimers or other non-target amplicons.

公开(公告)号：US20190256908A1

公开(公告)日：2019-08-22

申请号：US16399991

申请日：2019-04-30

申请人： Natera, Inc.

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

IPC分类号： C12Q1/6869 ,  C12Q1/6862 ,  C12Q1/6806 ,  G16B20/00 ,  C12Q1/6827 ,  C12Q1/6874 ,  C12Q1/6883

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.

公开(公告)号：US20150072872A1

公开(公告)日：2015-03-12

申请号：US14546321

申请日：2014-11-18

申请人： Natera, Inc.

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 ,  G06F19/00 ,  G06F19/18

CPC分类号： C12Q1/6883 ,  C12Q1/6827 ,  C12Q1/6869 ,  C12Q2537/161 ,  C12Q2537/165 ,  C12Q2600/112 ,  C12Q2600/156 ,  C12Q2600/16 ,  C12Q2600/172 ,  G06F19/34 ,  G16B5/00 ,  G16B20/00 ,  G16B30/00 ,  G16H50/30

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 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. 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： 本公开提供了用于从胎儿母体和胎儿的DNA样品测量的基因型数据以及来自母亲的基因型数据以及任选地还可以从父亲的基因型数据确定胎儿胎儿中染色体的倍性状态的方法 。 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。

公开(公告)号：US20140206552A1

公开(公告)日：2014-07-24

申请号：US14225356

申请日：2014-03-25

申请人： Natera, Inc.

发明人： Matthew Rabinowitz ,  Matthew Micah Hill ,  Bernhard Zimmerman ,  Johan Baner ,  Allison Ryan ,  George Gemelos

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6827 ,  C12Q1/6883 ,  C12Q2600/156 ,  G16B20/00 ,  G16B40/00 ,  C12Q2537/159 ,  C12Q2537/161 ,  C12Q2537/165

摘要： The present disclosure provides methods for determining the ploidy status of an embryo at a chromosome from a sample of DNA from an embryo. The ploidy state is determined by sequencing the DNA from one or more cells biopsied from the embryo, and analyzing the relative amounts of each allele at a plurality of polymorphic loci on the chromosome. In an embodiment, the ploidy state is determined by comparing the observed allele ratios to the expected allele ratios for different ploidy states. In an embodiment, the DNA is selectively amplified at a plurality of polymorphic loci by targeted sequencing. 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： 本公开提供了用于从胚胎的DNA样品测定染色体上胚胎的倍性状态的方法。 倍性状态通过对来自胚胎活检的一个或多个细胞的DNA进行测序，并分析染色体上多个多态性位点处的每个等位基因的相对量来确定。 在一个实施方案中，通过将观察到的等位基因比率与不同倍性状态的预期等位基因比率进行比较来确定倍性状态。 在一个实施方案中，通过靶向测序在多个多态位点选择性扩增DNA。 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。

公开(公告)号：US20240336970A1

公开(公告)日：2024-10-10

申请号：US18751153

申请日：2024-06-21

申请人： Natera, Inc.

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

IPC分类号： C12Q1/6883 ,  C12Q1/6809 ,  C12Q1/6811 ,  C12Q1/6844 ,  C12Q1/6848 ,  C12Q1/6851 ,  C12Q1/6855 ,  C12Q1/6869 ,  C12Q1/6874

CPC分类号： C12Q1/6883 ,  C12Q1/6809 ,  C12Q1/6811 ,  C12Q1/6844 ,  C12Q1/6848 ,  C12Q1/6851 ,  C12Q1/6855 ,  C12Q1/6869 ,  C12Q1/6874 ,  C12Q2600/156

摘要： The invention provides methods for simultaneously amplifying multiple nucleic acid regions of interest in one reaction volume as well as methods for selecting a library of primers for use in such amplification methods. The invention also provides library of primers with desirable characteristics, such as minimal formation of amplified primer dimers or other non-target amplicons.

公开(公告)号：US11591649B2

公开(公告)日：2023-02-28

申请号：US16796748

申请日：2020-02-20

申请人： Natera, Inc.

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

IPC分类号： C12Q1/6869 ,  G16B10/00 ,  C12Q1/6876 ,  C12Q1/6844

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.

公开(公告)号：US11408031B2

公开(公告)日：2022-08-09

申请号：US16012667

申请日：2018-06-19

申请人： Natera, Inc.

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

IPC分类号： C12Q1/68 ,  C12Q1/6869 ,  C12Q1/6876 ,  C12Q1/6844 ,  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.

公开(公告)号：US09163282B2

公开(公告)日：2015-10-20

申请号：US13791397

申请日：2013-03-08

申请人： Natera, Inc.

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 ,  C12Q1/68 ,  G06F19/18 ,  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。

公开(公告)号：US20130196862A1

公开(公告)日：2013-08-01

申请号：US13780022

申请日：2013-02-28

申请人： Natera, Inc.

发明人： Matthew Rabinowitz ,  Johan Baner ,  George Gemelos ,  Mathew M. Hill ,  Stymir Sigurjonsson

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6883 ,  C12Q1/6881 ,  C12Q2600/156 ,  G16B20/00

摘要： The invention provides methods for chromosome copy number calling on genetic samples, such as fetal samples subject to contamination from maternal DNA. The present disclosure provides methods for determining the ploidy status of a chromosome in a fetus (such as a gestating fetus or a POC sample) 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. In some embodiments, 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： 本发明提供了染色体拷贝数调用基因样品的方法，例如受母体DNA污染的胎儿样品。 本公开提供了从包含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中确定胎儿（例如胎儿胎儿或POC样品）中染色体的倍性状态的方法 ，以及来自母亲和父亲的基因型数据。 在一些实施方案中，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所测量的等位基因分布的模式进行比较来确定倍性状态 混合样品，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。