Effect of oligonucleotide truncation on single-nucleotide distinction by solid-phase hybridization

Anal Chem. 2002 Jan 1;74(1):199-202. doi: 10.1021/ac010555s.

Abstract

Oligonucleotide microarrays are used to analyze target sequences on the basis of differences in hybridization stability between matched and mismatched probe-target duplexes. DNA microarray manufacture via photolithographic synthesis generates a minority of full-length oligonucleotide probes along with a series of 5'-truncated contaminants. In a model experiment, we now investigate the effect of truncated oligonucleotides on the ability to distinguish target sequence variants that differ in a single nucleotide position. A series of oligonucleotides, mixed in proportions simulating stepwise synthetic yields of between 82 and 100%, were bound to a solid support and allowed to hybridize to a target molecule. The extent of hybridization was monitored over a range of temperatures via the fluorescence of a double-strand-specific dye. The discriminatory power of pure oligonucleotide probes was found to be significantly greater than that of a population of truncated probes, but only over a limited temperature interval. We conclude that at optimal temperatures greater oligonucleotide quality can improve the performance of oligonucleotide hybridization microarrays.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA Probes / chemistry
  • DNA Probes / standards*
  • Humans
  • Nucleic Acid Hybridization
  • Oligonucleotide Array Sequence Analysis / standards*
  • Oligonucleotides / chemistry
  • Oligonucleotides / standards

Substances

  • DNA Probes
  • Oligonucleotides