Noninvasive prenatal genotyping of fetal sex chromosomes

    公开(公告)号:US10152568B2

    公开(公告)日:2018-12-11

    申请号:US13978358

    申请日:2012-01-05

    IPC分类号: G06F19/18 C12Q1/6883

    摘要: Methods, apparatuses, and system are provided for analyzing a maternal sample to determine whether a male fetus of a pregnant female has inherited an X-linked mutation from the mother. A percentage of fetal DNA in the sample is obtained, and cutoff values for the two possibilities (fetus inherits mutant or normal allele) are determined. A proportion of mutant alleles relative to a normal allele on the X-chromosome can then be compared to the cutoff values to make a classification of which allele is inherited. Alternatively, a number of alleles from a target region on the X-chromosome can be compared to a number of alleles from a reference region on the X-chromosome to identify a deletion or amplification. The fetal DNA percentage can be computed by counting reactions with a fetal-specific allele, and correcting the number to account for a statistical distribution among the reactions.

    Detection of genetic or molecular aberrations associated with cancer
    6.
    发明授权
    Detection of genetic or molecular aberrations associated with cancer 有权
    检测与癌症相关的遗传或分子畸变

    公开(公告)号:US08741811B2

    公开(公告)日:2014-06-03

    申请号:US13308473

    申请日:2011-11-30

    IPC分类号: C40B30/02 C12Q1/68 G06F19/18

    摘要: Biological samples including cell-free DNA fragments are analyzed to identify imbalances in chromosomal regions, e.g., due to deletions and/or amplifications in a tumor. Multiple loci are used for each chromosomal region. Such imbalances can then be used to diagnose (screen) a patient for cancer, as well as prognosticate a patient with cancer, or to detect the presence or to monitor the progress of a premalignant condition in a patient. The severity of an imbalance as well as the number of regions exhibiting an imbalance can be used. A systematic analysis of non-overlapping segments of a genome can provide a general screening tool for a sample. Additionally, a patient can be tested over time to track severity of each of one or more chromosomal regions and a number of chromosomal regions to enable screening and prognosticating, as well as monitoring of progress (e.g. after treatment).

    摘要翻译: 分析包括无细胞DNA片段的生物样品,以鉴定染色体区域中的不平衡,例如由于肿瘤中的缺失和/或扩增。 每个染色体区域使用多个基因座。 然后可以将这种不平衡用于诊断(筛选)患者癌症,以及预测患有癌症的患者,或者检测病人的存在或监测恶化前状况的进展情况。 可以使用不平衡的严重性以及表现出不平衡的区域的数量。 对基因组的非重叠片段的系统分析可以为样品提供一般的筛选工具。 此外,可以随时间测试患者以跟踪一个或多个染色体区域和多个染色体区域中的每一个的严重性,以使得能够进行筛选和预测,以及监测进展(例如,治疗后)。

    Circulating mRNA as diagnostic markers
    7.
    发明授权
    Circulating mRNA as diagnostic markers 有权
    循环mRNA作为诊断标记

    公开(公告)号:US07829285B2

    公开(公告)日:2010-11-09

    申请号:US11807258

    申请日:2007-05-24

    摘要: Methods and kits are provided for diagnosing, monitoring, or predicting the conditions of pre-eclampsia, fetal chromosomal aneuploidy, and pre-term labor in a pregnant woman, as well as for detecting pregnancy in a woman, by quantitatively measuring in the maternal blood the amount of one or more mRNA species encoding human chorionic gonadotropin β subunit (hCG-β), human placental lactogen (hPL), human corticotropin releasing hormone (hCRH), KiSS-1 metastasis-suppressor (KISS1), tissue factor pathway inhibitor 2 (TPFI2), placenta-specific 1 (PLAC1), or glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and comparing the amount of the mRNA species with a standard control.

    摘要翻译: 提供方法和试剂盒,用于诊断,监测或预测孕妇的先兆子痫,胎儿染色体非整倍性和早产儿的状况,以及孕妇检测怀孕情况,通过定量测量母体血液 编码人绒毛膜促性腺激素的一种或多种mRNA种类的量; 亚单位(hCG-和bgr),人胎盘乳腺癌(hPL),促皮质激素释放激素(hCRH),KiSS-1转移抑制因子(KISS1),组织因子途径抑制剂2(TPFI2),胎盘特异性1(PLAC1) 或甘油醛-3-磷酸脱氢酶(GAPDH),并将mRNA种类的量与标准对照进行比较。

    Circulating mRNA as diagnostic markers
    8.
    发明申请
    Circulating mRNA as diagnostic markers 审中-公开
    循环mRNA作为诊断标记

    公开(公告)号:US20080153090A1

    公开(公告)日:2008-06-26

    申请号:US11807253

    申请日:2007-05-24

    IPC分类号: C12Q1/68

    摘要: Methods and kits are provided for diagnosing, monitoring, or predicting the conditions of pre-eclaimpsia, fetal chromosomal aneuploidy, and pre-term labor in a pregnant woman, as well as for detecting pregnancy in a woman, by quantitatively measuring in the maternal blood the amount of one or more mRNA species encoding human chorionic gonadotropin β subunit (hCG-β), human placental lactogen (hPL), human corticotropin releasing hormone (hCRH), KiSS-1 metastasis-suppressor (KISS1), tissue factor pathway inhibitor 2 (TPFI2), placenta-specific 1 (PLAC1), or glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and comparing the amount of the mRNA species with a standard control.

    摘要翻译: 提供方法和试剂盒,用于诊断,监测或预测怀孕妇女的pre-eclaimpsia,胎儿染色体非整倍性和早产儿的状况,以及通过定量测量孕妇血液中的孕妇检测怀孕情况 编码人绒毛膜促性腺激素β亚基(hCG-β),人胎盘乳腺癌(hPL),促皮质激素释放激素(hCRH),KiSS-1转移抑制因子(KISS1),组织因子途径抑制剂2 (TPFI2),胎盘特异性1(PLAC1)或甘油醛-3-磷酸脱氢酶(GAPDH),并将mRNA种类的量与标准对照进行比较。

    Size-based genomic analysis
    9.
    发明授权
    Size-based genomic analysis 有权
    基于大小的基因组分析

    公开(公告)号:US08620593B2

    公开(公告)日:2013-12-31

    申请号:US12940992

    申请日:2010-11-05

    IPC分类号: G06F19/00 G11C17/00 C12Q1/68

    摘要: Systems, methods, and apparatuses for performing a prenatal diagnosis of a sequence imbalance are provided. A shift (e.g. to a smaller size distribution) can signify an imbalance in certain circumstances. For example, a size distribution of fragments of nucleic acids from an at-risk chromosome can be used to determine a fetal chromosomal aneuploidy. A size ranking of different chromosomes can be used to determine changes of a rank of an at-risk chromosome from an expected ranking. Also, a difference between a statistical size value for one chromosome can be compared to a statistical size value of another chromosome to identify a significant shift in size. A genotype and haplotype of the fetus may also be determined using a size distribution to determine whether a sequence imbalance occurs in a maternal sample relative to a genotypes or haplotype of the mother, thereby providing a genotype or haplotype of the fetus.

    摘要翻译: 提供了用于执行序列不平衡的产前诊断的系统,方法和装置。 在某些情况下,偏移(例如,到更小的分布)可以表示不平衡。 例如,可以使用来自高危染色体的核酸片段的大小分布来确定胎儿染色体非整倍体。 可以使用不同染色体的大小排序来从预期排名中确定危险染色体的等级的变化。 而且,一个染色体的统计大小值之间的差异可以与另一个染色体的统计大小值进行比较,以确定大小的显着变化。 也可以使用大小分布来确定胎儿的基因型和单倍型,以确定相对于母体的基因型或单倍型,母体样品中是否发生序列不平衡,从而提供胎儿的基因型或单倍型。

    Fetal genomic analysis from a maternal biological sample
    10.
    发明授权
    Fetal genomic analysis from a maternal biological sample 有权
    母体生物样品的胎儿基因组分析

    公开(公告)号:US08467976B2

    公开(公告)日:2013-06-18

    申请号:US12940993

    申请日:2010-11-05

    IPC分类号: G06F19/00 C12Q1/68 G11C17/00

    摘要: Systems, methods, and apparatus for determining at least a portion of fetal genome are provided. DNA fragments from a maternal sample (maternal and fetal DNA) can be analyzed to identify alleles at certain loci. The amounts of DNA fragments of the respective alleles at these loci can be analyzed together to determine relative amounts of the haplotypes for these loci and determine which haplotypes have been inherited from the parental genomes. Loci where the parents are a specific combination of homozygous and heterozygous can be analyzed to determine regions of the fetal genome. Reference haplotypes common in the population can be used along with the analysis of the DNA fragments of the maternal sample to determine the maternal and paternal genomes. Determination of mutations, a fractional fetal DNA concentration in a maternal sample, and a proportion of coverage of a sequencing of the maternal sample can also be provided.

    摘要翻译: 提供了用于确定胎儿基因组的至少一部分的系统,方法和装置。 可以分析来自母体样品(母体和胎儿DNA)的DNA片段,以鉴定某些位点处的等位基因。 可以一起分析在这些位点处各个等位基因的DNA片段的量,以确定这些基因座的单倍型的相对量,并确定哪些单元型已经从亲代基因组遗传。 可以分析父母是纯合子和杂合子的特异性组合的位点,以确定胎儿基因组的区域。 可以在群体中常见的参考单倍型与母体样品的DNA片段的分析一起使用,以确定母体和父系的基因组。 也可以提供母体样品中突变的确定,胎儿DNA分数的分数以及母体样品测序的覆盖率。