NEWBORN SCREENING BY MULTIPLEX MOLECULAR ANALYSIS

通过多重分子分析进行新生儿筛查

• 批准号: 2869557
• 负责人: EDWIN W NAYLOR
• 金额: $ 8.61万
• 依托单位: PEDIATRIX SCREENING, INC.
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-03-01 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2869557
• 关键词: DNA primers; alpha 1 antitrypsin deficiency; biomedical automation; diagnosis design /evaluation; genetic disorder diagnosis; genetic screening; hemoglobinopathy; hereditary hemochromatosis; high performance liquid chromatography; human genetic material tag; mass screening; metabolism disorder diagnosis; mother /infant health care; newborn human (0-6 weeks); nucleic acid sequence; oligonucleotides; pediatrics; polymerase chain reaction

Neonatal screening is a proven public health service. Innovative methods such as tandem mass spectrometry have greatly increased the number of disorders effectively identified in newborn screening laboratories. To continue expanding the number of treatable disorders identified in newborns, a first tier, automated, multiplex molecular assay will be developed. The assay is based on DNA obtained from the universally collected neonatal blood card. A multiplex PCR assay will be developed to amplify DNA sequences that are diagnostic for the following disorders: sickle cell hemoglobinopathies S, C, and E alleles; alpha-1-Antitrypsin Deficiency S allele and Z allele; Factor V Leiden A1691G; and Hemochromatosis G845A. Analysis of PCR products will be performed using a low-density oligonucleotide array. The low-density oligonucleotide array will simultaneously distinguish both wild type and mutant alleles at the loci described. Data from the arrays will be processed using a BioScan Proximal Imaging System. Completing the Specific Aims of this proposal will demonstrate the feasibility of a first tier molecular screening protocol. The ability to simultaneously detect several disorders will make comprehensive newborn screening more affordable and a more effective public health service. PROPOSED COMMERCIAL APPLICATIONS: Neo Gen Screening provides a supplemental screening service, beyond that mandated by the state. Expanding the number of treatable disorders detected will make the service more comprehensive and thus more attractive to health care institutions. The screening services proposed are marketable for newborn screening and high-risk screening.

新生儿检查是一项行之有效的公共卫生服务。 创新的方法，如串联质谱法，大大增加了新生儿筛查实验室有效识别的疾病数量。为了继续扩大在新生儿中确定的可治疗疾病的数量，将开发第一层、自动化、多重分子测定。 该检测基于从普遍收集的新生儿血液卡中获得的DNA。 将开发一种多重PCR检测试剂盒，以扩增可诊断以下疾病的DNA序列：镰状细胞血红蛋白病S、C和E等位基因; α-1-抗胰蛋白酶缺乏症S等位基因和Z等位基因;因子V Leiden A1691 G;和血色病G845 A。 将使用低密度寡核苷酸阵列进行PCR产物分析。 低密度寡核苷酸阵列将同时区分所述基因座处的野生型和突变等位基因。 将使用BioScan近端成像系统处理来自阵列的数据。 完成本提案的具体目标将证明第一级分子筛选方案的可行性。 同时检测几种疾病的能力将使全面的新生儿筛查更负担得起，并成为更有效的公共卫生服务。拟议的商业应用：新基因筛选提供了一个补充筛选服务，超出了国家的授权。 扩大可治疗疾病的检测数量将使服务更加全面，从而对卫生保健机构更具吸引力。 拟议的筛查服务在新生儿筛查和高风险筛查方面是有市场的。

项目成果

Analysis of common mutations in the galactose-1-phosphate uridyl transferase gene: new assays to increase the sensitivity and specificity of newborn screening for galactosemia.

1-磷酸半乳糖尿苷基转移酶基因常见突变分析：提高新生儿半乳糖血症筛查敏感性和特异性的新测定方法。

• DOI: 10.1016/s1525-1578(10)60450-3
• 发表时间: 2003
• 期刊: The Journal of molecular diagnostics : JMD.
• 作者: Dobrowolski,StevenF;Banas,RichardA;Suzow,JosephG;Berkley,Michelle;Naylor,EdwinW
• 通讯作者: Naylor,EdwinW

A high throughput beta-globin genotyping method by multiplexed melting temperature analysis.

通过多重熔解温度分析的高通量 β-珠蛋白基因分型方法。

• DOI: 10.1016/j.ymgme.2003.12.007
• 发表时间: 2004
• 期刊: Molecular genetics and metabolism.
• 作者: Lin,Zhili;Suzow,JosephG;Fontaine,JamieM;Naylor,EdwinW
• 通讯作者: Naylor,EdwinW