Alternative titles; symbols
This entry is included in the database for historical reasons; the beta-related HpaI RFLP was the first to be discovered.
Kan and Dozy (1978) used the HpaI restriction polymorphism (really the linkage principle) to make the prenatal diagnosis of sickle cell anemia. When 'normal' DNA is digested with HpaI, the beta-globin gene is contained in a fragment 7.6 kilobases long. In persons of African extraction two variants were detected, 7.0 kb and 13.0 kb long. These variants resulted from alteration in the normal HpaI recognition site 5000 nucleotides to the 3-prime side of the beta-globin gene. The 7.6 and 7.0 kb fragments were present in persons with Hb A, while 87% of persons with Hb S had the 13.0 kb variant. Kurnit (1979) questioned that sufficient time had elapsed for 13% of the sickle gene to become associated with the 'normal' 7.6 kb HpaI polymorphism through crossing-over. Consequently, he suggested the sickle cell variant may have had more than one origin in Africa. Several other possibilities, particularly a much earlier origin of the sickle gene, cannot be excluded, however. The method is sufficiently sensitive that the cells in 15 ml of uncultured amniotic fluid sufficed. To avoid the cumbersome term 'restriction fragment length polymorphism' used by Botstein et al. (1980), Nei and Tajima (1981) suggested the term 'nucleon,' and for polymorphism therein the term 'nucleomorphs.' However, the term of Botstein et al. (1980), with the acronym RFLP (sometimes pronounced 'rif-lip'), has achieved general usage. Wilson (1984) was critical of the Botstein term because length polymorphism occurs with deletions and insertions, i.e., is one class of mutation. He suggested simply 'restriction fragment polymorphism.'
Botstein, D., White, R. L., Skolnick, M., Davis, R. W. Construction of a genetic linkage map in man using restriction fragment length polymorphisms. Am. J. Hum. Genet. 32: 314-331, 1980. [PubMed: 6247908]
Kan, Y. W., Dozy, A. M. Antenatal diagnosis of sickle-cell anaemia by DNA analysis of amniotic-fluid cells. Lancet 312: 910-912, 1978. Note: Originally Volume II. [PubMed: 81926] [Full Text: https://doi.org/10.1016/s0140-6736(78)91629-x]
Kan, Y. W., Dozy, A. M. Polymorphism of DNA sequence adjacent to human beta-globin structural gene: relationship to sickle mutation. Proc. Nat. Acad. Sci. 75: 5631-5635, 1978. [PubMed: 281713] [Full Text: https://doi.org/10.1073/pnas.75.11.5631]
Kurnit, D. M. Evolution of sickle variant gene. (Letter) Lancet 313: 104 only, 1979. Note: Originally Volume I. [PubMed: 84107] [Full Text: https://doi.org/10.1016/s0140-6736(79)90093-x]
Nei, M., Tajima, F. DNA polymorphism detectable by restriction endonucleases. Genetics 97: 145-163, 1981. [PubMed: 6266912] [Full Text: https://doi.org/10.1093/genetics/97.1.145]
Panny, S. R., Scott, A. F., Smith, K. D., Phillips, J. A., III, Kazazian, H. H., Jr., Talbot, C. C., Jr., Boehm, C. D. Population heterogeneity of the Hpa I restriction site associated with the beta-globin gene: implications for prenatal diagnosis. Am. J. Hum. Genet. 33: 25-35, 1981. [PubMed: 6162380]
Wilson, A. C. Personal Communication. Berkeley, Calif. 7/1984.