Detection of sickle cell beta S-globin allele by hybridization with synthetic oligonucleotides.

Abstract
Two 19-base-long oligonucleotides were synthesized, one complementary to the normal human .beta.-globin gene (.beta.A) and one complementary to the sickle cell .beta.-globin gene (.beta.S). The nonadecanucleotides were radioactively labeled and used as probes in DNA hybridization. Under appropriate hybridization conditions, these probes can be used to distinguish the .beta.A gene from the .beta.S allele. The DNA from individuals homozygous for the normal .beta.-globin gene (.beta.A.beta.A) only hybridized with the .beta.A-specific probe; the DNA from those homozygous for the sickle cell .beta.-globin gene (.beta.S.beta.S) only hybridized with the .beta.S-specific probe. The DNA from heterozygous individuals (.beta..ALPHA..beta.S) hybridized with both probes. This allele-specific hybridization behavior of oligonucleotides provides a general method for diagnosis of any genetic disease which involves a point mutation in the DNA sequence of a single-copy gene.