The sickle cell mutation is a single nucleotide substitution (A to T) at codon 6 in the b -globin gene, resulting in a GAG (Glu) to GTG (Val) substitution. The example shows how one can design ASOs: one specific for the normal (b ^A) allele and identical to a sequence of 19 nucleotides encompassing codons 3-9 of this allele, and one specific for the mutant (b ^S) allele, being identical to the equivalent sequence of the mutant allele. The labeled ASOs can be individually hybridized to denatured genomic DNA samples on dot-blots. The b ^A- and b ^S-specific ASOs can hybridize to the complementary antisense strand of the normal and mutatnt alleles respectively, forming perfect 19-bp duplexes. However, duplexes between the b ^A-specific ASO and the b ^S allele, or between the b ^S-specific ASO and the b ^A allele have a single mismatch and are unstable at high hybridization stringency.