公开(公告)号：US20150072872A1

公开(公告)日：2015-03-12

申请号：US14546321

申请日：2014-11-18

Applicant: Natera, Inc.

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

IPC: C12Q1/68 ,  G06F19/00 ,  G06F19/18

CPC classification number: 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

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.

Abstract translation: 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

Applicant: Natera, Inc.

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

IPC: C12Q1/68

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

Abstract: 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.

Abstract translation: 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：US20140154682A1

公开(公告)日：2014-06-05

申请号：US14080656

申请日：2013-11-14

Applicant: Natera, Inc.

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

IPC: G06F19/18

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

Abstract translation: 本文公开了用于在非侵入性产前诊断的上下文中确定胎儿中染色体的拷贝数的方法。 在一个实施方案中，分析来自含有胎儿DNA和母体DNA的遗传物质的样品的测量的遗传数据以及来自胎儿的生物亲本的遗传数据，并确定感兴趣的染色体的拷贝数。 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进行与胎儿有关的临床决定。

公开(公告)号：US12270073B2

公开(公告)日：2025-04-08

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 ,  C12P19/34 ,  C12Q1/6806 ,  C12Q1/6827 ,  C12Q1/686 ,  C12Q1/6862 ,  C12Q1/6869 ,  C12Q1/6874 ,  C12Q1/6883 ,  G01N33/48 ,  G16B20/00 ,  G16B20/10 ,  G16B20/20 ,  G16B20/40 ,  C12N15/11 ,  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：US12260934B2

公开(公告)日：2025-03-25

申请号：US16677017

申请日：2019-11-07

Applicant: Natera, Inc.

Inventor： Styrmir Sigurjonsson ,  Naresh Vankayalapati ,  Allison Ryan ,  Zachary Demko ,  Milena Banjevic

IPC: G01N33/48 ,  G16B5/00 ,  G16B5/20 ,  G16B20/00 ,  G16B20/10 ,  G16B30/00 ,  G16H10/40

Abstract: Provided herein are improved methods for detecting aneuploidy in a sample. The methods in certain embodiments are used for the analysis of circulating DNA in serum samples, such as circulating fetal DNA or circulating tumor DNA. In certain embodiments, chromosome or chromosome segments of interest are used to set a bias model and/or a control value for a z-score determination, in illustrative examples without the use of a control chromosome.

公开(公告)号：US11746376B2

公开(公告)日：2023-09-05

申请号：US16796748

申请日：2020-02-20

Applicant: Natera, Inc.

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

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

CPC classification number: C12Q1/6869 ,  C12Q1/6844 ,  C12Q1/6876 ,  G16B10/00 ,  C12Q2600/156

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：US11339429B2

公开(公告)日：2022-05-24

申请号：US16411770

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 ,  C12Q1/6862 ,  G16B20/00 ,  C12Q1/6874 ,  C12Q1/6883 ,  C12Q1/6827 ,  G16B20/10 ,  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：US11326208B2

公开(公告)日：2022-05-10

申请号：US17320540

申请日：2021-05-14

Applicant: Natera, Inc.

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

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

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：US11322224B2

公开(公告)日：2022-05-03

申请号：US14532666

申请日：2014-11-04

Applicant: Natera, Inc.

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

IPC: C12Q1/68 ,  G16B20/00 ,  C12Q1/6827 ,  C12Q1/6862 ,  C12Q1/686 ,  G16B20/10 ,  G16B20/20 ,  G16B20/40 ,  C12Q1/6883 ,  C12Q1/6869 ,  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：US11286530B2

公开(公告)日：2022-03-29

申请号：US17196822

申请日：2021-03-09

Applicant: Natera, Inc.

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

IPC: C12Q1/68 ,  C12Q1/6883 ,  C12Q1/6809 ,  C12Q1/6811 ,  C12Q1/6844 ,  C12Q1/6851 ,  C12Q1/6855 ,  C12Q1/6869 ,  C12Q1/6874 ,  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.