Skip to main content
PMC home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1988 Jun;42(6):808–815.

A test of the heterozygote-advantage hypothesis in cystic fibrosis carriers.

L B Jorde 1, G M Lathrop 1
PMCID: PMC1715197  PMID: 3369446

Abstract

We report a test of the hypothesis that the high frequency of cystic fibrosis (CF) in Caucasian populations is due to a fertility advantage in CF carriers. One hundred forty-three grandparent couples of Utah CF cases were compared with 20 replicate sets of matched control couples drawn from the Utah Genealogical Database. Ascertainment correction, which has not been applied in previous studies of CF carrier fertility, was applied to these data. Before ascertainment correction was applied, CF carriers appeared to manifest a significant fertility advantage over controls. After the correction formula was applied, this difference disappeared. Carriers and controls were also compared in terms of the length of intervals between births. Again, no significant differences were found. It was concluded that fertility differences are unlikely to account for the observed Caucasian CF gene frequency. Other mechanisms, particularly a past selective event or random genetic drift, are more likely to be responsible.

Full text

PDF
808

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Beaudet A., Bowcock A., Buchwald M., Cavalli-Sforza L., Farrall M., King M. C., Klinger K., Lalouel J. M., Lathrop G., Naylor S. Linkage of cystic fibrosis to two tightly linked DNA markers: joint report from a collaborative study. Am J Hum Genet. 1986 Dec;39(6):681–693. [PMC free article] [PubMed] [Google Scholar]
  2. Bowcock A. M., Crandall J., Daneshvar L., Lee G. M., Young B., Zunzunegui V., Craik C., Cavalli-Sforza L. L., King M. C. Genetic analysis of cystic fibrosis: linkage of DNA and classical markers in multiplex families. Am J Hum Genet. 1986 Dec;39(6):699–706. [PMC free article] [PubMed] [Google Scholar]
  3. Burdick A. B. Frequency of the gene for cystic fibrosis with a view of replacement and recognition effects and reproduction by homozygotes. Hum Hered. 1977;27(5):366–371. doi: 10.1159/000152892. [DOI] [PubMed] [Google Scholar]
  4. Cassano W. F. Cystic fibrosis and the plague. Med Hypotheses. 1985 Sep;18(1):51–52. doi: 10.1016/0306-9877(85)90119-7. [DOI] [PubMed] [Google Scholar]
  5. Conneally P. M., Merritt A. D., Yu P. L. Cystic fibrosis: population genetics. Tex Rep Biol Med. 1973 Winter;31(4):639–650. [PubMed] [Google Scholar]
  6. Danks D. M., Allan J., Phelan P. D., Chapman C. Mutations at more than one locus may be involved in cystic fibrosis--evidence based on first-cousin data and direct counting of cases. Am J Hum Genet. 1983 Sep;35(5):838–844. [PMC free article] [PubMed] [Google Scholar] [Retracted]
  7. Danks D. M., Phelan P. D., Chapman C. Retraction: No evidence for more than one locus in cystic fibrosis . Am J Hum Genet. 1984 Nov;36(6):1401–1402. [PMC free article] [PubMed] [Google Scholar]
  8. Edwards J. H. Heterozygote advantage. Arch Dis Child. 1977 May;52(5):343–344. doi: 10.1136/adc.52.5.343. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. GOODMAN H. O., REED S. C. Heredity of fibrosis of the pancreas; possible mutation rate of the gene. Am J Hum Genet. 1952 Jun;4(2):59–71. [PMC free article] [PubMed] [Google Scholar]
  10. Gedschold J., Kropf S., Szibor R., Berger M. Cystic fibrosis--a single locus disease? Results of a population genetics study. Hum Genet. 1987 Mar;75(3):277–280. doi: 10.1007/BF00281074. [DOI] [PubMed] [Google Scholar]
  11. Hallett W. Y., Knudson A. G., Jr, Massey F. J., Jr Absence of detrimental effect of the carrier state for the cystic fibrosis gene. Am Rev Respir Dis. 1965 Nov;92(5):714–724. doi: 10.1164/arrd.1965.92.5.714. [DOI] [PubMed] [Google Scholar]
  12. Hollander D. H. Etiogenesis of the European cystic fibrosis polymorphism: heterozygote advantage against venereal syphilis? Med Hypotheses. 1982 Feb;8(2):191–197. doi: 10.1016/0306-9877(82)90102-5. [DOI] [PubMed] [Google Scholar]
  13. Klinger K., Stanislovitis P., Hoffman N., Watkins P. C., Schwartz R., Doherty R., Scambler P., Farrall M., Williamson R., Wainwright B. Genetic homogeneity of cystic fibrosis. Nucleic Acids Res. 1986 Nov 11;14(21):8681–8686. doi: 10.1093/nar/14.21.8681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Knudson A. G., Jr, Wayne L., Hallett W. Y. On the selective advantage of cystic fibrosis heterozygotes. Am J Hum Genet. 1967 May;19(3 Pt 2):388–392. [PMC free article] [PubMed] [Google Scholar]
  15. Lander E. S., Botstein D. Consanguinity and heterogeneity: cystic fibrosis need not be homogeneous in Italy. Am J Hum Genet. 1986 Aug;39(2):282–283. [PMC free article] [PubMed] [Google Scholar]
  16. Mayo O. On the maintenance of polymorphisms having an inviable homozygote. Ann Hum Genet. 1970 Jan;33(3):307–317. doi: 10.1111/j.1469-1809.1970.tb01655.x. [DOI] [PubMed] [Google Scholar]
  17. Meindl R. S. Hypothesis: a selective advantage for cystic fibrosis heterozygotes. Am J Phys Anthropol. 1987 Sep;74(1):39–45. doi: 10.1002/ajpa.1330740104. [DOI] [PubMed] [Google Scholar]
  18. Pritchard D. J., Hickman G. R., Nelson R. Sex ratio and heterozygote advantage in cystic fibrosis families. Arch Dis Child. 1983 Apr;58(4):290–293. doi: 10.1136/adc.58.4.290. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Romeo G., Bianco M., Devoto M., Menozzi P., Mastella G., Giunta A. M., Micalizzi C., Antonelli M., Battistini A., Santamaria F. Incidence in Italy, genetic heterogeneity, and segregation analysis of cystic fibrosis. Am J Hum Genet. 1985 Mar;37(2):338–349. [PMC free article] [PubMed] [Google Scholar]
  20. Romeo G., Devoto M., Bianco M. Homogeneity vs. heterogeneity of cystic fibrosis in Italy. Am J Hum Genet. 1986 Aug;39(2):283–284. [PMC free article] [PubMed] [Google Scholar]
  21. Schmidtke J., Krawczak M., Schwartz M., Alkan M., Bonduelle M., Bühler E., Chemke M., Darnedde T., Domagk J., Engel W. Linkage relationships and allelic associations of the cystic fibrosis locus and four marker loci. Hum Genet. 1987 Aug;76(4):337–343. doi: 10.1007/BF00272441. [DOI] [PubMed] [Google Scholar]
  22. Shier W. T. Increased resistance to influenza as a possible source of heterozygote advantage in cystic fibrosis. Med Hypotheses. 1979 Jun;5(6):661–667. doi: 10.1016/0306-9877(79)90087-2. [DOI] [PubMed] [Google Scholar]
  23. Steinberg A. G., Brown D. C. On the Incidence of Cystic Fibrosis of the Pancreas. Am J Hum Genet. 1960 Dec;12(4 Pt 1):416–424. [PMC free article] [PubMed] [Google Scholar]
  24. Stuart A. B., Burdon M. G. Letter: Frequency of cystic-fibrosis gene. Lancet. 1974 Dec 21;2(7895):1521–1521. doi: 10.1016/s0140-6736(74)90264-5. [DOI] [PubMed] [Google Scholar]
  25. Super M., van Schalkwyk D. J. Heterozygote advantage in cystic fibrosis: mosquito tests. Clin Genet. 1979 Aug;16(2):65–68. doi: 10.1111/j.1399-0004.1979.tb00853.x. [DOI] [PubMed] [Google Scholar]
  26. Ten Kate L. P. A method for analysing fertility of heterozygotes for autosomal recessive disorders, with special reference to cystic fibrosis, Tay-Sachs disease and phenylketonuria. Ann Hum Genet. 1977 Jan;40(3):287–297. doi: 10.1111/j.1469-1809.1977.tb00193.x. [DOI] [PubMed] [Google Scholar]
  27. Vitale E., Devoto M., Mastella G., Romeo G. Homogeneity of cystic fibrosis in Italy. Am J Hum Genet. 1986 Dec;39(6):832–836. [PMC free article] [PubMed] [Google Scholar]
  28. Watkins P. C., Schwartz R., Hoffman N., Stanislovitis P., Doherty R., Klinger K. A linkage study of cystic fibrosis in extended multigenerational pedigrees. Am J Hum Genet. 1986 Dec;39(6):735–743. [PMC free article] [PubMed] [Google Scholar]
  29. White R. The search for the cystic fibrosis gene. Science. 1986 Nov 28;234(4780):1054–1055. doi: 10.1126/science.3465037. [DOI] [PubMed] [Google Scholar]
  30. Wright S. W., Morton N. E. Genetic studies on cystic fibrosis in Hawaii. Am J Hum Genet. 1968 Mar;20(2):157–169. [PMC free article] [PubMed] [Google Scholar]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics

RESOURCES