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Nucleic Acids Research, 2002, Vol. 30, No. 19 e100
© 2002 Oxford University Press

LNA-enhanced detection of single nucleotide polymorphisms in the apolipoprotein E

Nana Jacobsen*,1, Joan Bentzen3, Michael Meldgaard2, Mogens Havsteen Jakobsen1,2, Mogens Fenger3, Sakari Kauppinen1 and Jan Skouv1

1 Department of LNA Microarrays, 2 Department of Chemistry, Exiqon, Bygstubben 9, DK-2950 Vedbaek, Denmark and 3 Department of Clinical Biochemistry, University Hospital of Copenhagen, DK-2650 Hvidovre, Denmark

*To whom correspondence should be addressed. Tel: +45 45 66 08 88; Fax: +45 45 66 18 88; Email: jacobsen{at}exiqon.com

Genotyping of single nucleotide polymorphisms (SNPs) in large populations presents a great challenge, especially if the SNPs are embedded in GC-rich regions, such as the codon 112 SNP in the human apolipoprotein E (apoE). In the present study, we have used immobilized locked nucleic acid (LNA) capture probes combined with LNA-enhancer oligonucleotides to obtain efficient and specific interrogation of SNPs in the apoE codons 112 and 158, respectively. The results demonstrate the usefulness of LNA oligonucleotide capture probes combined with LNA enhancers in mismatch discrimination. The assay was applied to a panel of patient samples with simultaneous genotyping of the patients by DNA sequencing. The apoE genotyping assays for the codons 112 and 158 SNPs resulted in unambiguous results for all patient samples, concurring with those obtained by DNA sequencing.


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