Method and mixture reagents for analyzing the nucleotide sequence of nucleic acids by mass spectrometry

US6218118A · kind A · utility

Assignee

• AGILENT TECHNOLOGIES, INC. · US

Inventors

• Jeffrey R. Sampson · San Jose, US
• Zohar Yakhini · Palo Alto, US
• Peter Webb · Menlo Park, US
• Nicholas M. Sampas · San Jose, US
• Anna M. Tsalenko · Chicago, US
• Joel Myerson · Berkeley, US

Key dates

• Filing date: Jul 9, 1998
• Grant date: Apr 17, 2001
• Expiry date: Jul 9, 2018

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C40B40/00
• WIPO field: Biotechnology
• WIPO sector: Chemistry

Abstract

Methods and reagents are disclosed which satisfy the need for more sensitive, more accurate and higher through-put analyses of target nucleic acid sequences. The methods and reagents may be generically applied to generally any target nucleic acid sequence and do not require a priori information about the presence, location or identity of mutations in the target nucleic acid sequence. The reagents of the invention are mixtures of natural and mass-modified oligonucleotide precursors having a high level of coverage and mass number complexity. A method is also disclosed for analyzing a target nucleic acid sequence employing the mixtures of natural and mass-modified oligonucleotide precursors and chemical or enzymatic assays to alter the mass of the oligonucleotide precursors prior to mass spectral analysis, generally via MALDI-TOF. The enzymatic assay may be a polymerase extension assay or a ligase assay. The kits for carrying out the methods of the invention are also disclosed.