公开(公告)号：US10522242B2

公开(公告)日：2019-12-31

申请号：US15343003

申请日：2016-11-03

申请人： Natera, Inc.

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

IPC分类号： G01N33/50 ,  G16B30/00 ,  G16B20/00 ,  C12Q1/6827 ,  C12Q1/6874 ,  C12Q1/6876 ,  C12Q1/6883 ,  G06N7/00

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.

公开(公告)号：US20190323076A1

公开(公告)日：2019-10-24

申请号：US16444619

申请日：2019-06-18

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

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：US20190309359A1

公开(公告)日：2019-10-10

申请号：US16418104

申请日：2019-05-21

申请人： Natera, Inc.

发明人： Bernhard ZIMMERMANN ,  Ryan SWENERTON ,  Matthew RABINOWITZ ,  Styrmir SIGURJONSSON ,  George GEMELOS ,  Apratim GANGULY ,  Himanshu SETHI

IPC分类号： C12Q1/6869 ,  C12Q1/6806

摘要： The present disclosure provides methods and compositions for sequencing nucleic acid molecules and identifying individual sample nucleic acid molecules using Molecular Index Tags (MITs). Furthermore, reaction mixtures, kits, and adapter libraries are provided.

公开(公告)号：US20190309358A1

公开(公告)日：2019-10-10

申请号：US16395154

申请日：2019-04-25

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 ,  C12Q1/6827 ,  C12Q1/6874 ,  C12Q1/6806 ,  C12Q1/6883 ,  C12Q1/6862 ,  G16B20/00

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：US20190276888A1

公开(公告)日：2019-09-12

申请号：US16411585

申请日：2019-05-14

申请人： Natera, Inc.

发明人： Matthew RABINOWITZ ,  Milena BANJEVIC ,  Zachary DEMKO ,  David JOHNSON ,  Dusan KIJACIC ,  Dimitri PETROV ,  Joshua SWEETKIND-SINGER ,  Jing XU

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

摘要： 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：US20190264277A1

公开(公告)日：2019-08-29

申请号：US16411770

申请日：2019-05-14

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：US20190256912A1

公开(公告)日：2019-08-22

申请号：US16399911

申请日：2019-04-30

申请人： Natera, Inc.

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

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

摘要： 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：US20190249241A1

公开(公告)日：2019-08-15

申请号：US16289528

申请日：2019-02-28

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

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.

公开(公告)号：US10351906B2

公开(公告)日：2019-07-16

申请号：US15336630

申请日：2016-10-27

申请人： Natera, Inc.

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

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

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：US10266893B2

公开(公告)日：2019-04-23

申请号：US15881384

申请日：2018-01-26

申请人： Natera, Inc.

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

IPC分类号： C12Q1/6848 ,  C12Q1/6851 ,  C12Q1/6855 ,  C12Q1/6876 ,  C12Q1/6883 ,  G06N7/00 ,  G06F19/18 ,  G06F19/24

摘要： 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.