公开(公告)号：US11332785B2

公开(公告)日：2022-05-17

申请号：US16412043

申请日：2019-05-14

Applicant: Natera, Inc.

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

IPC: C12Q1/6869 ,  C12Q1/6806 ,  C12Q1/686 ,  C12Q1/6883 ,  G16B20/00 ,  C12Q1/6862 ,  C12Q1/6874 ,  C12Q1/6827 ,  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：US11155861B2

公开(公告)日：2021-10-26

申请号：US16399991

申请日：2019-04-30

Applicant: Natera, Inc.

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

IPC: C12Q1/00 ,  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：US11072826B2

公开(公告)日：2021-07-27

申请号：US16012667

申请日：2018-06-19

Applicant: Natera, Inc.

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

IPC: C12Q1/68 ,  C12Q1/6869 ,  C12Q1/6876 ,  C12Q1/6844 ,  G16B10/00

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：US10711309B2

公开(公告)日：2020-07-14

申请号：US16399931

申请日：2019-04-30

Applicant: Natera, Inc.

Inventor： Matthew Rabinowitz ,  Milena Banjevic ,  Zachary Demko ,  David Johnson

IPC: C12Q1/6883 ,  C12Q1/6827 ,  G16B20/00 ,  G16B25/00 ,  G16B30/00 ,  G16B40/00 ,  C12Q1/6876

Abstract: 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.

公开(公告)号：US10590482B2

公开(公告)日：2020-03-17

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.

公开(公告)号：US10392664B2

公开(公告)日：2019-08-27

申请号：US15881488

申请日：2018-01-26

Applicant: Natera, Inc.

Inventor： Matthew Rabinowitz ,  Milena Banjevic ,  Zachary Demko ,  David Johnson ,  Dusan Kijacic ,  Dimitri Petrov ,  Joshua Sweetkind-Singer ,  Jing Xu

IPC: C12Q1/6848 ,  C12Q1/6851 ,  C12Q1/6855 ,  C12Q1/6883 ,  C12Q1/6876 ,  G06N7/00 ,  G16B20/00 ,  G16B40/00

Abstract: Disclosed herein is a system and method for increasing the fidelity of measured genetic data, for making allele calls, and for determining the state of aneuploidy, in one or a small set of cells, or from fragmentary DNA, where a limited quantity of genetic data is available. Poorly or incorrectly measured base pairs, missing alleles and missing regions are reconstructed using expected similarities between the target genome and the genome of genetically related individuals. In accordance with one embodiment, incomplete genetic data from an embryonic cell are reconstructed at a plurality of loci using the more complete genetic data from a larger sample of diploid cells from one or both parents, with or without haploid genetic data from one or both parents. In another embodiment, the chromosome copy number can be determined from the measured genetic data, with or without genetic information from one or both parents.

公开(公告)号：US10227652B2

公开(公告)日：2019-03-12

申请号：US15187555

申请日：2016-06-20

Applicant: Natera, Inc.

Inventor： Matthew Rabinowitz ,  Milena Banjevic ,  Zachary Demko ,  David Johnson

IPC: G01N33/48 ,  C12Q1/6883 ,  C12Q1/6827 ,  G06F19/20 ,  G06F19/18 ,  G06F19/22 ,  C12Q1/6876 ,  G06F19/24

Abstract: 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.

公开(公告)号：US10061890B2

公开(公告)日：2018-08-28

申请号：US15243915

申请日：2016-08-22

Applicant: Natera, Inc.

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

IPC: G06F19/22 ,  G06F19/18 ,  C12Q1/6827 ,  C12Q1/6874 ,  C12Q1/6876 ,  C12Q1/6883 ,  G06N7/00

CPC classification number: G16B30/00 ,  C12Q1/6827 ,  C12Q1/6874 ,  C12Q1/6876 ,  C12Q1/6883 ,  C12Q2600/156 ,  C12Q2600/16 ,  G06N7/005 ,  G16B20/00 ,  C12Q2537/16 ,  C12Q2537/165

Abstract: 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.

公开(公告)号：US10061889B2

公开(公告)日：2018-08-28

申请号：US14983128

申请日：2015-12-29

Applicant: Natera, Inc.

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

IPC: G06F19/22 ,  G06F19/18 ,  C12Q1/6827 ,  C12Q1/6874 ,  C12Q1/6876 ,  C12Q1/6883 ,  G06N7/00

CPC classification number: G16B30/00 ,  C12Q1/6827 ,  C12Q1/6874 ,  C12Q1/6876 ,  C12Q1/6883 ,  C12Q2600/156 ,  C12Q2600/16 ,  G06N7/005 ,  G16B20/00 ,  C12Q2537/16 ,  C12Q2537/165

Abstract: 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.

公开(公告)号：US09695477B2

公开(公告)日：2017-07-04

申请号：US15293257

申请日：2016-10-13

Applicant: Natera, Inc.

Inventor： Matthew Rabinowitz ,  Milena Banjevic ,  Zachary Demko ,  David Johnson

IPC: G01N33/48 ,  G01N31/00 ,  G06G7/48 ,  G06G7/58 ,  C12Q1/68 ,  G06F19/20 ,  G06F19/18 ,  G06F19/22 ,  G06F19/24

CPC classification number: C12Q1/6883 ,  C12Q1/6827 ,  C12Q1/6876 ,  C12Q2600/118 ,  C12Q2600/156 ,  C12Q2600/158 ,  G06F19/18 ,  G06F19/20 ,  G06F19/22 ,  G06F19/24 ,  C12Q2537/16 ,  C12Q2537/165

Abstract: 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.