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    • 26. 发明申请
    • Haplotype markers for diagnosing susceptibility to immunological conditions
    • 用于诊断免疫条件易感性的单倍型标记
    • US20050266432A1
    • 2005-12-01
    • US11069908
    • 2005-02-28
    • Arnold OliphantSarah Murray
    • Arnold OliphantSarah Murray
    • C12Q1/68
    • C12Q1/6883C12Q2600/156C12Q2600/172
    • The invention provides a method of identifying a SNP haplotype that correlates with an HLA type, MHC allele or susceptibility to a particular disease or condition including the steps of (a) providing the identity of the nucleotide for each of a set of single nucleotide polymorphism (SNPs) in the major histocompatability complex (MHC) region in a population of individuals; (b) providing the HLA type, MHC allele, or susceptibility to the particular disease or condition for the individuals; and (c) identifying a SNP haplotype in the population that correlates with the HLA type, MHC allele or susceptibility to the particular disease or condition, wherein the SNP haplotype includes the SNPs in the MHC region. The invention further provides a method for predicting an HLA type, MHC allele or susceptibility to a particular disease or condition of an individual including the steps of (a) providing the identity of a plurality of SNPs in one or more nucleic acids from the individual that correlate with an HLA type, MHC allele or susceptibility to a particular disease or condition; and (b) predicting the HLA type, MHC genotype or susceptibility to a particular disease or condition for the individual based on a SNP haplotype comprising the plurality of SNPs. The invention also provides SNPs and oligonucleotide probes that are useful for identifying haplotypes associated with a particular disease or condition or with the presence of particular protein variants involved in immunological recognition. The SNPs and probes are also useful for predicting HLA-type, HLA genotype or susceptibility to a particular disease or condition.
    • 本发明提供了鉴定与特定疾病或病症的HLA类型,MHC等位基因或易感性相关的SNP单倍型的方法,包括以下步骤:(a)提供一组单核苷酸多态性中的每一个的核苷酸的身份( SNPs)在个体人群中的主要组织相容性复合体(MHC)区域; (b)为个体提供HLA类型,MHC等位基因或对特定疾病或病症的易感性; 和(c)识别与HLA类型,MHC等位基因或对特定疾病或病症的易感性相关的群体中的SNP单倍型,其中所述SNP单倍型包括MHC区域中的SNP。 本发明还提供了一种用于预测HLA类型,MHC等位基因或对个体的特定疾病或病症的易感性的方法,包括以下步骤:(a)在个体的一个或多个核酸中提供多个SNP的身份, 与HLA类型,MHC等位基因或对特定疾病或病症的易感性相关; 和(b)基于包含多个SNP的SNP单元型,预测HLA类型,MHC基因型或对个体的特定疾病或病症的易感性。 本发明还提供可用于鉴定与特定疾病或病症相关的单倍型或涉及免疫学识别的特定蛋白质变体的存在的SNP和寡核苷酸探针。 SNP和探针也可用于预测HLA型,HLA基因型或对特定疾病或病症的易感性。
    • 27. 发明授权
    • Method for sequencing both strands of a double stranded DNA in a single sequencing reaction
    • 在单次测序反应中测序双链DNA两条链的方法
    • US06251610B1
    • 2001-06-26
    • US09664560
    • 2000-09-18
    • Jamila GupteArnold Oliphant
    • Jamila GupteArnold Oliphant
    • C12P1934
    • C12N15/10C12Q1/686C12Q1/6869C12Q2535/119
    • A method is presented which uses a unique opposite strand joining strategy during PCR of an original DNA to generate a product which, when sequenced with a single sequencing primer yields the sequence of both strands of the original DNA. The PCR primers include 1) a modified oligomer corresponding to the 5′ end of a first strand of the DNA to be amplified wherein said modified oligomer includes the reverse complementary sequence to a sequence within said first strand of DNA and a specific PCR priming sequence which will specifically hybridize to a portion of the DNA to be amplified and 2) a second oligomer corresponding to the 5′ end of the second strand of the DNA to be amplified and which contains the priming sequence for the second strand of the DNA and will specifically hybridize to a portion of the DNA to be amplified. During PCR an intermediate product is formed where one end of one strand loops around to hybridize to its complement on the same strand. This results in a hairpin structure which elongates using its own strand as a template to form a double sized product that contains the sequence of both original strands. Upon denaturation this yields single strands with the single strands having the sequence of both of the original strands included in tandem. Sequencing these single strands using a single primer, e.g., a primer complementary to the second oligomer, yields the sequences of both strands of the DNA of interest.
    • 提出了一种在原始DNA的PCR期间使用独特的相反链连接策略以产生产物的方法,当用单个测序引物测序时,产生原始DNA的两条链的序列。 PCR引物包括1)对应于待扩增的DNA的第一链的5'端的修饰的寡聚体,其中所述修饰的寡聚体包括与所述第一链DNA内的序列的反向互补序列和特异性PCR引物序列, 将与要扩增的DNA的一部分特异性杂交,以及2)对应于待扩增的DNA的第2链的5'末端的第二寡聚体,其含有第二链的引物序列, 与要扩增的DNA的一部分杂交。 在PCR期间,形成中间产物,其中一条链的一端环绕在与相同链上的其互补体杂交。 这导致发夹结构,其使用其自身的链作为模板延长以形成包含两条原始链的序列的双重尺寸的产物。 变性时,这产生单链,单链具有串联包含的两条原始链的序列。 使用单一引物(例如与第二寡聚体互补的引物)测序这些单链,产生目的DNA的两条链的序列。