Summary
Three polymorphic DNA marker loci (INT1L1, D7S23 and D7S399) map to a chromosomal region that is very close to the cystic fibrosis (CF) locus in terms of genetic distance. These marker loci have been used to analyse the linkage disequilibrium in 137CF families from two South European countries (Italy and Spain). The markers can be analysed for differences in linkage disequilibrium more easily in these populations than in North Europeans, in whom the disequilibrium between the allelic systems defined by the probes and CF is much greater and on a “plateau” through the genetic region. The different levels of disequilibrium found in the studied populations suggest that D7S399 and D7S23 are both closer to CF than INT1L1, and provide additional information on the origins and homogeneity of the CF defect.
Similar content being viewed by others
References
Beaudet A, Bowcock A, Buchwald M, Cavalli-Sforza L, Farrall M, King MC, Klinger K, Lalouel JL, Lathrop G, Naylor S, Ott J, Tsui LC, Wainwright B, Watkings P, White R, Williamson R (1986) Linkage of cystic fibrosis to two tightly linked DNA markers: joint report from a collaborative study. Am J Hum Genet 39:681–693
Beaudet AL, Spence JL, Montes M, O'Brien M, Estivill X, Farrall M, Williamson R (1988) Experience with new DNA markers for diagnosis of cystic fibrosis. N Engl J Med 318:50–51
Bodmer WF (1972) Population genetics of the HLA system: retrospect and prospect. In: Dausset J, Colombani J (eds) Histocompatibility testing. Munksgaard, Copenhagen, pp 611–617
Chakravarti A, Bueton KH, Antonarakis SE, Waber PG, Boehm CD, Kazazian HH (1984) Nonuniform recombination within the human β-globin gene cluster. Am J Hum Genet 36:1239–1258
Estivill X, Schmidtke J, Williamson R, Wainwright BJ (1986) chromosome assignment and restriction fragment length polymorphism analysis of the anonymous DNA probe B79a at 7q22 (HGM8 assignment D7S13). Hum Genet 74:320–322
Estivill X, Farrall M, Scambler PJ, Bell G, Hawley KMF, Lench NJ, Bates GP, Kruyer HC, Frederick PA, Stanier P, Watson EK, Williamson R, Wainwright BJ (1987a) A candidate for the cystic fibrosis locus isolated by selection for methylation-free islands. Nature 326:840–845
Estivill X, Scambler PJ, Wainwright BJ, Hawley K, Frederick P, Baiget M, Kere J, Williamson R, Farrall M (1987b) Patterns of polymorphism and linkage disequilibrium for cystic fibrosis. Genomics 1:257–263
Estivill X, Farrall M, Williamson R, Ferrari M, Seia M, Giunta AM, Novelli G, Potenza L, Dallapiccola B, Borgo G, Gasparini P, Pignatti PF, De Benedetti L, Vitale E, Devoto M, Romeo G (1988) Linkage disequilibrium between cystic fibrosis and linked DNA markers in Italian families: a collaborative study. Am J Hum Genet 43:23–28
Estivill X, McLean C, Nunes V, Casals T, Gallano P, Scambler P, Williamson R (1989) Isolation of a new DNA marker in linkage disequilibrium with cystic fibrosis situated between J3.11 (D7S8) and IRP. Am J Hum Genet 44:704–710
Farrall M, Estivill X, Williamson R (1987) Cystic fibrosis: indirect carrier detection. Lancet II:156–157
Farrall M, Wainwright BJ, Feldman GL, Beaudet A, Sretenovic Z, Halley, Simon M, Dickerman L, Devoto M, Romeo G, Kaplan JC, Kitzis A, Williamson R (1988) Recombinations between IRP and cystic fibrosis. Am J Hum Genet 43:471–475
Feinberg A, Vogelstein B (1984) A technique for radiolabelling DNA fragments to high specific activity. Anal Biochem 137:266–267
Hill WG, Robertson A (1968) Linkage disequilibrium in finite populations. Theor Appl Genet 38:226–231
Knowlton RG, Cohen-Haguenauer O, Van Cong N, Frazel J, Brown VA, Barker D, Braman JC, Schumm JW, Tsui LC, Buchwald M, Donis-Keller H (1985) A polymorphic DNA marker linked to cystic fibrosis is located on chromosome 7. Nature 318:380–382
Krawczak M, Konecki DS, Schmidtke J, Dück M, Nützenadel W, Trefz FK (1988) Allelic association of the cystic fibrosis locus and two DNA markers, XV-2c and KM.19, in 55 German families. Hum Genet 80:78–80
Lathrop GM, Farrall M, O'Connell P, Wainwright B, Leppert M, Nakamura Y, Lench N, Kruyer H, Dean M, Park M, Vande Woude G, Lalouel JM, Williamson R, White R (1988) Refined linkage map of chromosome 7 in the region of the cystic fibrosis gene. Am J Hum Genet 42:38–44
Maniatis T, Fritsch EF, Sambrook J (eds) (1982) Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY
Scambler PJ, Wainwright BJ, Watson E, Bates G, Bell G, Williamson R, Farrall M (1986) Isolation of a further anonymous informative DNA sequence from chromosome seven closely linked to cystic fibrosis. Nucleic Acids Res 14:1951–1956
Thompson MW (1980) Genetics of cystic fibrosis. In: Sturgess JM (ed) Perspectives in cystic fibrosis. Canadican Cystic Fibrosis Foundation, Toronto, pp 281–291
Tsui LC, Buchwald M, Barker D, Braman JC, Knowlton R, Schumm JW, Eiberg H, Mohr J, Kennedy D, Plasvic N, Zsiga M, Markiewicz D, Akots G, Brown V, Helms C, Gravius T, Parker C, Rediker K, Donnis-Keller H (1985) Cystic fibrosis locus defined by a genetically linked polymorphic DNA marker. Science 230:1054–1057
Wainwright BJ, Scambler PJ, Schmidtke J, Watson EK, Law HY, Farrall M, Cooke HJ, Eiberg H, Williamson R (1985) Localization of cystic fibrosis locus to human chromosome 7cen-q22. Nature 318:384–385
Wainwright BJ, Scambler PJ, Stanier P, Watson EK, Bell G, Wicking C, Estivill X, Courtney M, Boue A, Pedersen PS, Williamson R, Farrall M (1988) Isolation of a human gene with protein sequence similarity to human and murine int-1 and the Drosophila segment polarity mutant wingless. EMBO J 7:1743–1748
White R, Woodward S, Leppert M, O'Connell P, Hoff M, Herbst J, Lalouel JM, Dean M, Vande Woude GF (1985) A closely linked marker for cystic fibrosis. Nature 318:382–384
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Estivill, X., Gasparini, P., Novelli, G. et al. Linkage disequilibrium for DNA haplotypes near the cystic fibrosis locus in two South European populations. Hum Genet 83, 175–178 (1989). https://doi.org/10.1007/BF00286713
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00286713