公开(公告)号：US09163282B2

公开(公告)日：2015-10-20

申请号：US13791397

申请日：2013-03-08

Applicant: Natera, Inc.

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

IPC: G01N33/48 ,  G01N31/00 ,  G06G7/48 ,  G06G7/58 ,  C12Q1/68 ,  G06F19/18 ,  G06F19/24

CPC classification number: C12Q1/6869 ,  C12Q1/6806 ,  C12Q1/6827 ,  C12Q1/6862 ,  C12Q1/6874 ,  C12Q1/6883 ,  C12Q2600/156 ,  G06F19/18 ,  G06F19/24 ,  C12Q2537/161 ,  C12Q2537/165

Abstract: 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.

Abstract translation: 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：US12020778B2

公开(公告)日：2024-06-25

申请号：US16361511

申请日：2019-03-22

Applicant: Natera, Inc.

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

IPC: G16B20/00 ,  C12Q1/6806 ,  C12Q1/6827 ,  C12Q1/686 ,  C12Q1/6862 ,  C12Q1/6869 ,  C12Q1/6874 ,  C12Q1/6883 ,  G16B20/10 ,  G16B20/20 ,  G16B20/40 ,  G16B40/00

CPC classification number: G16B20/00 ,  C12Q1/6806 ,  C12Q1/6827 ,  C12Q1/686 ,  C12Q1/6862 ,  C12Q1/6869 ,  C12Q1/6874 ,  C12Q1/6883 ,  G16B20/10 ,  G16B20/20 ,  G16B20/40 ,  C12Q2525/179 ,  C12Q2527/113 ,  C12Q2527/143 ,  C12Q2537/143 ,  C12Q2537/149 ,  C12Q2537/159 ,  C12Q2545/114 ,  C12Q2600/156 ,  C12Q2600/16 ,  G16B40/00 ,  C12Q1/6827 ,  C12Q2537/161 ,  C12Q2537/165 ,  C12Q1/686 ,  C12Q2537/143

Abstract: 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：US11482300B2

公开(公告)日：2022-10-25

申请号：US17494745

申请日：2021-10-05

Applicant: Natera, Inc.

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

IPC: C12Q1/68 ,  G16B20/00 ,  G16B20/20 ,  G16B20/40 ,  G16B20/10 ,  C12Q1/6806 ,  C12Q1/6827 ,  C12Q1/686 ,  C12Q1/6862 ,  C12Q1/6869 ,  C12Q1/6874 ,  C12Q1/6883 ,  G16B40/00

Abstract: 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：US11450408B2

公开(公告)日：2022-09-20

申请号：US17494745

申请日：2021-10-05

Applicant: Natera, Inc.

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

IPC: C12Q1/68 ,  G16B20/00 ,  G16B20/20 ,  G16B20/40 ,  G16B20/10 ,  C12Q1/6806 ,  C12Q1/6827 ,  C12Q1/686 ,  C12Q1/6862 ,  C12Q1/6869 ,  C12Q1/6874 ,  C12Q1/6883 ,  G16B40/00

Abstract: 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：US11306357B2

公开(公告)日：2022-04-19

申请号：US14179399

申请日：2014-02-12

Applicant: Natera, Inc.

Inventor： Matthew Rabinowitz ,  George Gemelos ,  Milena Banjevic ,  Allison Ryan ,  Zachary Demko ,  Matthew Hill ,  Bernhard Zimmerman ,  Johan Baner

IPC: C12Q1/68 ,  C12Q1/6883 ,  G16B5/00 ,  G16B20/00 ,  G16B30/00 ,  C12Q1/6827 ,  G16H10/40 ,  C12Q1/6855 ,  C12Q1/686 ,  G16B5/20 ,  G16B20/10 ,  G16B20/20 ,  G16B20/40 ,  G16B30/10 ,  C12Q1/6869 ,  G16H50/30

Abstract: 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.

公开(公告)号：US11198905B2

公开(公告)日：2021-12-14

申请号：US16795973

申请日：2020-02-20

Applicant: Natera, Inc.

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

IPC: C12Q1/68 ,  G01N33/48 ,  C12P19/34 ,  C12Q1/6869 ,  G16B20/00 ,  C12Q1/6827 ,  C12Q1/6862 ,  C12Q1/686 ,  G16B20/10 ,  G16B20/20 ,  G16B20/40 ,  C12Q1/6883 ,  C12Q1/6806 ,  C12Q1/6874 ,  G16B40/00

Abstract: 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：US11180808B2

公开(公告)日：2021-11-23

申请号：US14179399

申请日：2014-02-12

Applicant: Natera, Inc.

Inventor： Matthew Rabinowitz ,  George Gemelos ,  Milena Banjevic ,  Allison Ryan ,  Zachary Demko ,  Matthew Hill ,  Bernhard Zimmerman ,  Johan Baner

IPC: C12Q1/68 ,  C12Q1/6883 ,  G16B5/00 ,  G16B20/00 ,  G16B30/00 ,  C12Q1/6827 ,  G16H10/40 ,  C12Q1/6855 ,  C12Q1/686 ,  G16B5/20 ,  G16B20/10 ,  G16B20/20 ,  G16B20/40 ,  G16B30/10 ,  C12Q1/6869 ,  G16H50/30

Abstract: 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.

公开(公告)号：US10774380B2

公开(公告)日：2020-09-15

申请号：US16287662

申请日：2019-02-27

Applicant: Natera, Inc.

Inventor： Allison Ryan ,  Styrmir Sigurjonsson ,  Milena Banjevic ,  George Gemelos ,  Matthew Hill ,  Johan Baner ,  Matthew Rabinowitz ,  Zachary Demko

IPC: C12Q1/6869 ,  G16B10/00 ,  C12Q1/6876

Abstract: 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：US10597709B2

公开(公告)日：2020-03-24

申请号：US16412301

申请日：2019-05-14

Applicant: Natera, Inc.

Inventor： Bernhard Zimmermann ,  Matthew Hill ,  Philippe Lacroute ,  Michael Dodd ,  Alexander Wong

IPC: C12Q1/68 ,  C12Q1/686 ,  C12Q1/6874 ,  C12Q1/6883 ,  C12Q1/6811 ,  C12Q1/6848

Abstract: 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：US20190256907A1

公开(公告)日：2019-08-22

申请号：US16399957

申请日：2019-04-30

Applicant: Natera, Inc.

Inventor： Allison Ryan ,  Styrmir Sigurjonsson ,  Milena Banjevic ,  George Gemelos ,  Matthew Hill ,  Johan Baner ,  Matthew Rabinowitz ,  Zachary Demko

IPC: C12Q1/6869 ,  G16B10/00 ,  C12Q1/6876

Abstract: 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.