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.

公开(公告)号：US10011870B2

公开(公告)日：2018-07-03

申请号：US15372279

申请日：2016-12-07

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： C12Q1/68 ,  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：US20180173846A1

公开(公告)日：2018-06-21

申请号：US15887914

申请日：2018-02-02

申请人： Natera, Inc.

发明人： Styrmir SIGURJONSSON ,  Naresh VANKAYALAPATI ,  Allison RYAN ,  Zachary DEMKO ,  Milena BANJEVIC

IPC分类号： G06F19/22 ,  G06F19/12

CPC分类号： G16B30/00 ,  G16B5/00 ,  G16B20/00 ,  G16H10/40

摘要： 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：US20180155792A1

公开(公告)日：2018-06-07

申请号：US15881488

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： C12Q1/6883 ,  C12Q1/6851 ,  G06F19/24 ,  G06F19/18 ,  C12Q1/6848 ,  G06N7/00

CPC分类号： C12Q1/6876 ,  C12Q1/6848 ,  C12Q1/6851 ,  C12Q1/6855 ,  C12Q1/6883 ,  C12Q2600/156 ,  C12Q2600/158 ,  G06N7/005 ,  G16B20/00 ,  G16B40/00 ,  C12Q2525/155 ,  C12Q2535/122 ,  C12Q2537/16

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：US20180032670A1

公开(公告)日：2018-02-01

申请号：US15724020

申请日：2017-10-03

申请人： Natera, Inc.

发明人： Matthew RABINOWITZ ,  Allison RYAN ,  George GEMELOS ,  Milena BANJEVIC ,  Zachary DEMKO

IPC分类号： G06F19/22 ,  G06F19/18 ,  G06N7/00 ,  C12Q1/68

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

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：US20170242960A1

公开(公告)日：2017-08-24

申请号：US15586013

申请日：2017-05-03

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： G06F19/18 ,  C12Q1/68

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：US20170029893A1

公开(公告)日：2017-02-02

申请号：US15293257

申请日：2016-10-13

申请人： Natera, Inc.

发明人： Matthew Rabinowitz ,  Milena Banjevic ,  Zachary Demko ,  David Johnson

IPC分类号： C12Q1/68 ,  G06F19/22

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

摘要： 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.

摘要翻译： 公开了一种用于确定一个或一小组细胞遗传数据的系统和方法，或从有限数量的遗传数据获得的片段DNA。 使用已知方法获取和扩增目标个体的遗传数据，并且使用目标基因组与基因相关受试者的基因组之间的预期相似性重建差测量的碱基对，缺失的等位基因和缺失区域。 根据本发明的一个实施方案，从母体血液中分离的胚胎细胞，胎儿细胞或无细胞胎儿DNA获得不完整的遗传数据，并且使用更大的样本的更完整的遗传数据来重建不完整的遗传数据 来自一个或两个父母的二倍体细胞，具有或不具有来自一个或两个亲本的单倍体细胞的遗传数据和/或从其他相关个体获取的遗传数据。

公开(公告)号：US20160369346A1

公开(公告)日：2016-12-22

申请号：US15252795

申请日：2016-08-31

申请人： Natera, Inc.

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

IPC分类号： C12Q1/68 ,  G06F19/22

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

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：US09499870B2

公开(公告)日：2016-11-22

申请号：US14498629

申请日：2014-09-26

申请人： Natera, Inc.

发明人： Joshua Babiarz ,  Bernhard Zimmermann

IPC分类号： C12Q1/68 ,  C12N15/10

CPC分类号： C12Q1/6886 ,  C12N15/10 ,  C12Q1/6806 ,  C12Q1/6883 ,  C12Q2521/301 ,  C12Q2537/16 ,  C12Q2545/113 ,  C12Q2600/16 ,  C12Q2600/166 ,  Y10T436/10

摘要： Embodiments of the invention include methods and compositions for producing proficiency testing standards for noninvasive prenatal genetic diagnostics and for the detection and monitoring of cancer. The compositions can include a plurality of different nucleosomal DNA fragments derived from either primary cells or cell lines. The amount of the different nucleosomal DNA fragments can be varied so as to simulate naturally occurring cell free DNA samples obtained from the blood of the pregnant woman or naturally occurring cell free DNA samples obtained from the blood of cancer patients.

摘要翻译： 本发明的实施方案包括用于生产非侵入性产前遗传诊断能力检测标准和检测和监测癌症的方法和组合物。 组合物可以包含衍生自原代细胞或细胞系的多个不同的核小体DNA片段。 可以改变不同核小体DNA片段的量，以模拟从孕妇的血液中获得的天然存在的无细胞DNA样品或从癌症患者的血液获得的天然存在的无细胞DNA样品。