Enzymatic Amplification of β-Globin Genomic Sequences and Restriction Site Analysis for Diagnosis of Sickle Cell Anemia
This paper reported the first published application of in vitro primer-mediated enzymatic amplification of DNA—the technique that became known as the polymerase chain reaction (PCR)—as part of a rapid, sensitive prenatal diagnostic test for sickle cell anemia. The authors amplified specific β-globin target sequences from genomic DNA roughly 220,000-fold and then distinguished the normal (βA) and sickle (βS) alleles by restriction endonuclease digestion of a hybridized end-labeled oligonucleotide probe. The combined procedure allowed genotyping in under a day using far less than one microgram of genomic DNA.