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Cystic fibrosis in Afro-Brazilians: XK haplotypes analysis supports the European origin of p.F508del mutation

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Abstract

Cystic fibrosis (CF) is a common autosomal recessive disorder, being the p.F508del the most frequent mutation. Also, a nearby restriction fragment length polymorphism (RFLP) named XK (KM19 and XV2C) is non-randomly associated with specific CF alleles. Our aim was to analyze the occurrence of the p.F508del mutation and XK haplotypes in Afro-Brazilians CF patients and controls, since these data is available for the other two main ethnic groups found in Brazil (Euro-Brazilians and Brazilian Amerindians), contributing for the whole comprehension of these haplotypes in the Brazilian population. A total of 103 patients and 54 controls were studied. PCR and PCR-RFLP methodologies were used to identify the presence of the p.F508del and the XK haplotype in the subjects. The combined data show that 84.2% of p.F508del mutation is associated with haplotype B and only 15.8% with haplotype A; no other haplotypes were found to be associated with this mutation. Our data suggest that the occurrence of p.F508del mutation and haplotype B in Afro-Brazilian patients occurs probably due to admixture with Euro-descendants. Therefore this mutation and haplotype could be used as a admixture marker.

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References

  • Azevêdo ES (1980) Subgroup studies of black admixture within a mixed population of Bahia, Brazil. Ann Hum Genet 44(Pt 1):55–60

    Article  PubMed  Google Scholar 

  • Beaudet AL, Feldman GL, Fernbach SD, Buffone GJ, O’Brien WE (1989) Linkage disequilibrium, cystic fibrosis, and genetic counseling. Am J Hum Genet 44(3):319–332

    CAS  PubMed  PubMed Central  Google Scholar 

  • Brazilian Institute of Geography and Statistics (2010) Census (2010). http://censo2010.ibge.gov.br/

  • Brazilian Study Group of Cystic Fibrosis (2012) Brazilian Cystic fibrosis patient registry: 2012 annual report. http://www.gbefc.org.br/gbefc/Registro_Ingles.pdf

  • Cabello GMK, Cabello PH, Lopez-Camelo JS, Llerena JC, Fernandes O (2005) Haplotype distribution of and linkage disequilibrium between four polymorphic markers near the CFTR locus in Brazilian cystic fibrosis patients. Hum Biol 77(6):853–865

    Article  PubMed  Google Scholar 

  • Cooper DN, Clayton JF (1988) DNA polymorphism and the study of disease associations. Hum Genet 78(4):299–312

    Article  CAS  PubMed  Google Scholar 

  • Costa FMM, Santana MA, Lemos ACM, Galvão-Castro B, Acosta AX (2007) Low frequency of the deltaAF508 mutation of the CFTR gene in a highly admixed population in Bahia, Brazil. Hum Biol 79(3):293–297

    Article  Google Scholar 

  • Cutting GR, Antonarakis SE, Buetow KH, Kasch LM, Rosenstein BJ, Kazazian HH (1989) Analysis of DNA polymorphism haplotypes linked to the cystic fibrosis locus in North American black and Caucasian families supports the existence of multiple mutations of the cystic fibrosis gene. Am J Hum Genet 44(3):307–318

    CAS  PubMed  PubMed Central  Google Scholar 

  • Denter M, Ramsay M, Jenkins T (1992) Cystic fibrosis. Part I. Frequency of the delta F508 mutation in South African families with cystic fibrosis. S Afr Med J 82(1):7–10

    CAS  PubMed  Google Scholar 

  • Estivill X, Scambler PJ, Wainwright BJ, Hawley K, Frederick P, Schwartz M et al (1987a) Patterns of polymorphism and linkage disequilibrium for cystic fibrosis. Genomics 1(3):257–263

  • Estivill X, Farrall M, Scambler PJ, Bell GM, Hawley KM, Lench NJ et al (1987b) A candidate for the cystic fibrosis locus isolated by selection for methylation-free islands. Nature 326(6116):840–845

  • Estivill X, Farrall M, Williamson R, Ferrari M, Seia M, Giunta AM et al (1988) Linkage disequilibrium between cystic fibrosis and linked DNA polymorphisms in Italian families: a collaborative study. Am J Hum Genet 43(1):23–28

    CAS  PubMed  PubMed Central  Google Scholar 

  • Horn GT, Richards B, Merrill JJ, Klinger KW (1990) Characterization and rapid diagnostic analysis of DNA polymorphisms closely linked to the cystic fibrosis locus. Clin Chem 36(9):1614–1619

    CAS  PubMed  Google Scholar 

  • Kerem B, Rommens JM, Buchanan JA, Markiewicz D, Cox TK, Chakravarti A et al (1989) Identification of the cystic fibrosis gene: genetic analysis. Science 245(4922):1073–1080

    Article  CAS  PubMed  Google Scholar 

  • Klein H (2002) As origens africanas dos escravos brasileiros. In: Pena SDJ (ed) Homo brasilis: Aspectos Genéticos, Lingüísticos, Históricos e Sócio-Antropológicos da Formação do Povo Brasileiro. FUNPEC, Ribeirão Preto, São Paulo

    Google Scholar 

  • Knowlton RG, Cohen-Haguenauer O, Van Cong N, Frézal J, Brown VA, Barker D et al (1985) A polymorphic DNA marker linked to cystic fibrosis is located on chromosome 7. Nature 318(6044):380–382

    Article  CAS  PubMed  Google Scholar 

  • Krieger H, Morton NE, Mi MP, Azevêdo E, Freire-Maia A, Yasuda N (1965) Racial admixture in north-eastern Brazil. Ann Hum Genet 29(2):113–125

    Article  CAS  PubMed  Google Scholar 

  • Lucotte G, Barré E, David F (1989) Linkage disequilibrium between cystic fibrosis and linked DNA polymorphisms at two DNA markers, XV-2c and KM. 19, in North African families. Am J Hum Genet 45(4):635–637

    CAS  PubMed  PubMed Central  Google Scholar 

  • Martin RK, Kaplan GC, Hodge TW, Barker PE (1988) Cystic fibrosis DNA markers in Alabama blacks. Genomics 3(4):385–388

    Article  CAS  PubMed  Google Scholar 

  • Miller M (1997) RXC: a program for the analysis of contingency tables via the metropolis algorithm computer. http://www.marksgeneticsoftware.net/rxc.htm

  • Morral N, Bertranpetit J, Estivill X, Nunes V, Casals T, Giménez J et al (1994) The origin of the major cystic fibrosis mutation (∆F508) in the European population. Nat Genet 7:169–175

    Article  CAS  PubMed  Google Scholar 

  • Raskin S, Phillips JA, Krishnamani MR, Vnencak-Jones C, Parker RA, Rozov T et al (1997a) Cystic fibrosis in the Brazilian population: DF508 mutation and KM-19/XV-2C haplotype distribution. Hum Biol 69(4):499–508

  • Raskin S, Philips JA, Krishnamani MR, Vnencak-Jones C, Parker RA, Dawson E et al (1997b) Regional distribution of cystic fibrosis-linked DNA haplotypes in Brazil: multicenter study. Hum Biol 69(1):75–88

  • Raskin S, Pereira L, Reis F, Rosario NA, Ludwig N, Valentim L et al (2003) High allelic heterogeneity between Afro-Brazilians and Euro-Brazilians impacts cystic fibrosis genetic testing. Genet Test 7(3):213–218

    Article  CAS  PubMed  Google Scholar 

  • Raskin S, Petzl-Erler ML, Phillips JA, Pereira-Ferrari L, Probst CM, Faucz FR et al (2007) Cystic fibrosis gene variability in two southern Brazilian Amerindian populations: analysis of the deltaF508 mutation and the KM19 and XV2C haplotypes. Hum Biol 79(1):79–91

    Article  CAS  PubMed  Google Scholar 

  • Raskin S, Pereira-Ferrari L, Reis FC, Abreu F, Marostica P, Rozov T et al (2008) Incidence of cystic fibrosis in five different states of Brazil as determined by screening of p.F508del, mutation at the CFTR gene in newborns and patients. J Cyst Fibros 7(1):15–22

    Article  CAS  PubMed  Google Scholar 

  • Riordan JR, Rommens JM, Kerem B, Alon N, Rozmahel R, Grzelczak Z et al (1989) Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science 245(4922):1066–1073

    Article  CAS  PubMed  Google Scholar 

  • Rommens JM, Iannuzzi MC, Kerem B, Drumm ML, Melmer G, Dean M et al (1989) Identification of the cystic fibrosis gene: chromosome walking and jumping. Science 245(4922):1059–1065

    Article  CAS  PubMed  Google Scholar 

  • Salas A, Richards M, Lareu M-V, Scozzari R, Coppa A, Torroni A et al (2004) The African diaspora: mitochondrial DNA and the Atlantic slave trade. Am J Hum Genet 74(3):454–465

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Salzano FM, Freire-Maia N (1967) Populações Brasileiras: Aspectos demográficos, genéticos e antropológicos. Companhia Editora Nacional, São Paulo

    Google Scholar 

Download references

Acknowledgements

We thank Diane Cooper, MSLS, NIH Library, for providing assistance in writing this manuscript. This research was supported in part by National Institutes of Health through Grants DK35592 and HD28819 (awarded to John A. Phillips III) and by DECIT/CNPq (Science and Technology Department of Ministry of Health) through a grant to Salmo Raskin.

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Authors and Affiliations

  1. Group for Advanced Molecular Investigation (NIMA), School of Health and Biosciences, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Paraná, Brazil

    D. A. S. de Souza, F. R. Faucz, R. B. de Alexandre, V. S. Sotomaior & S. Raskin

  2. Functional Genomics Laboratory, Carlos Chagas Institute, Oswaldo Cruz Foundation, Curitiba, Paraná, Brazil

    D. A. S. de Souza

  3. Section on Endocrinology and Genetics, Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD, 20892, USA

    F. R. Faucz

  4. Octávio Mangabeira Hospital, Reference Center of Cystic Fibrosis, Salvador, Bahia, Brazil

    M. A. Santana

  5. Pediatric Division, Federal University of Bahia, Salvador, Bahia, Brazil

    E. L. S. de Souza

  6. Pneumology Division, Department of Pediatrics, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

    F. J. C. Reis

  7. Department of Biomedicine, UniBrasil, Curitiba, Paraná, Brazil

    L. Pereira-Ferrari & L. Culpi

  8. Division of Medical Genetics and Genomic Medicine, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN, USA

    J. A. Phillips III

  9. 61H Travessa Chile, São José dos Pinhais, Paraná, 83035-200, Brazil

    D. A. S. de Souza

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  1. D. A. S. de Souza
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  2. F. R. Faucz
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  3. R. B. de Alexandre
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  4. M. A. Santana
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  5. E. L. S. de Souza
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  6. F. J. C. Reis
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  7. L. Pereira-Ferrari
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  8. V. S. Sotomaior
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  9. L. Culpi
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  10. J. A. Phillips III
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  11. S. Raskin
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Correspondence to D. A. S. de Souza.

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de Souza, D.A.S., Faucz, F.R., de Alexandre, R.B. et al. Cystic fibrosis in Afro-Brazilians: XK haplotypes analysis supports the European origin of p.F508del mutation. Genetica 145, 19–25 (2017). https://doi.org/10.1007/s10709-016-9942-x

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  • DOI: https://doi.org/10.1007/s10709-016-9942-x

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