公开(公告)号：US20180025109A1

公开(公告)日：2018-01-25

申请号：US15727428

申请日：2017-10-06

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：US20170076038A1

公开(公告)日：2017-03-16

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： G06F19/22 ,  G06F19/18 ,  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：US09430611B2

公开(公告)日：2016-08-30

申请号：US14092457

申请日：2013-11-27

申请人： Natera, Inc.

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

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

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获得不完全遗传数据，并且使用更大的样本二倍体的更完整的遗传数据重建不完整的遗传数据 来自一个或两个亲本的细胞，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：US20150051087A1

公开(公告)日：2015-02-19

申请号：US14532666

申请日：2014-11-04

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： C12Q1/68

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.

摘要翻译： 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：US20140162269A1

公开(公告)日：2014-06-12

申请号：US14179399

申请日：2014-02-12

申请人： Natera, Inc.

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

IPC分类号： C12Q1/68

CPC分类号： 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

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 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：US20140100134A1

公开(公告)日：2014-04-10

申请号：US14100928

申请日：2013-12-09

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： G06F19/12

CPC分类号： C12Q1/6883 ,  C12Q1/6827 ,  C12Q1/6869 ,  C12Q2537/161 ,  C12Q2537/165 ,  C12Q2600/112 ,  C12Q2600/156 ,  C12Q2600/16 ,  C12Q2600/172 ,  G06F19/00 ,  G06F19/12 ,  G06F19/18 ,  G06F19/22 ,  G06F19/34 ,  G16H50/30

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 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.

摘要翻译： 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。