Allele-specific ligation and recombinase polymerase amplification for the detection of single nucleotide polymorphisms

[EN] A novel multiplex detection of single nucleotide polymorphisms (SNPs), with point-of-care testing as its aim, is reported for supporting pharmacogenetic-based decisions. The strategy relies on allele-specific ligation to discriminate base sequence variations at the SNP site and the extension of...

Descripción completa

Detalles Bibliográficos
Autores: Lázaro-Zaragozá, Ana, Yamanaka, Eric-Seiti, Maquieira, Angel|||0000-0003-4641-4957, Tortajada-Genaro, Luis Antonio|||0000-0003-4021-5607
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Universitat Politècnica de València (UPV)
Repositorio:RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia
Idioma:inglés
OAI Identifier:oai:riunet.upv.es:10251/141435
Acceso en línea:https://riunet.upv.es/handle/10251/141435
Access Level:acceso abierto
Palabra clave:Universal RPA
Ligation
SNP
Optical sensor
Hybridization chip
Personalised healthcare
QUIMICA ANALITICA
Descripción
Sumario:[EN] A novel multiplex detection of single nucleotide polymorphisms (SNPs), with point-of-care testing as its aim, is reported for supporting pharmacogenetic-based decisions. The strategy relies on allele-specific ligation to discriminate base sequence variations at the SNP site and the extension of generated products by isothermal amplification and recombinase polymerase amplification (RPA). Having demonstrated the assay principle, the variables for the adequate integration of the ligation-amplification process were studied and compared to a conventional PCR approach. One key result was the development of RPA in a universal format using short-length primers, which enabled detection based on selective hybridisation on a barcode-DNA chip and a low-cost optical sensor. As proof of concept, we successfully discriminated genetic variants related to cardiovascular diseases and the adequate prescription of oral anticoagulant antagonists of vitamin K (genes CYP2C9 and VKROC1).