Abstract
We have previously mapped a locus controlling Plasmodium falciparum blood infection levels (PFBI) to chromosome 5q31–q33. We genotyped 19 microsatellite markers on chromosome 5q31–q33 in a new sample of 44 pedigrees comprising 84 nuclear families and 292 individuals living in a P. falciparum endemic area. Using a nonparametric multipoint variance-component approach (by GENEHUNTER), we evidenced a peak of linkage close to D5S636 (P=0.0069), with a heritability of 0.46. Using a variance-component method for linkage-disequilibrium mapping of quantitative traits (by QTDT) and the Bonferroni correction for multiple testing, we further detected allelic association in the presence of linkage between blood infection levels and D5S487 (P=6 × 10−5; Pc=0.0011), which is located on the distal part of the peak. These results confirm the importance of chromosome 5q31–q33 in the genetic control of PFBI levels.
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References
Haldane JBS . The rate of mutation of human genes. Proc. VIII Int Cong. Genet. Hereditas 1949; 35: 267–273.
Hill AV . The immunogenetics of human infectious diseases. Annu Rev Immunol 1998; 16: 593–617.
Kwiatkowski D . Genetic susceptibility to malaria getting complex. Curr Opin Genet Dev 2000; 10: 320.
Abel L, Cot M, Mulder L, Carnevale P, Feingold J . Segregation analysis detects a major gene controlling blood infection levels in human malaria. Am J Hum Genet 1992; 50: 1308–1317.
Garcia A, Cot M, Chippaux JP et al. Genetic control of blood infection levels in human malaria: evidence for a complex genetic model. Am J Trop Med Hyg 1998; 58: 480–488.
Rihet P, Abel L, Traore Y, Traore-Leroux T, Aucan C, Fumoux F . Human malaria: segregation analysis of blood infection levels in a suburban area and a rural area in Burkina Faso. Genet Epidemiol 1998; 15: 435–450.
Jepson A, Sisay JF, Banya W et al. Genetic linkage of mild malaria to the major histocompatibility complex in Gambian children: study of affected sibling pairs. BMJ 1997; 315: 96–97.
Kun JF, Mordmuller B, Lell B, Lehman LG, Luckner D, Kremsner PG . Polymorphism in promoter region of inducible nitric oxide synthase gene and protection against malaria. Lancet 1998; 351: 265–266.
Aucan C, Traore Y, Fumoux F, Rihet P . Familial correlation of immunoglobulin G subclass responses to Plasmodium falciparum antigens in Burkina Faso. Infect Immun 2001; 69: 996–1001.
Migot-Nabias F, Mombo LE, Luty AJ et al. Human genetic factors related to susceptibility to mild malaria in Gabon. Gene Immun 2000; 1: 435–441.
Sjoberg K, Lepers JP, Raharimalala L et al. Genetic regulation of human anti-malarial antibodies in twins. Proc Natl Acad Sci U S A 1992; 89: 2101–2104.
Stirnadel HA, Beck HP, Alpers MP, Smith TA . Genetic analysis of IgG subclass responses against RESA and MSP2 of Plasmodium falciparum in adults in Papua New Guinea. Epidemiol Infect 2000; 124: 153–162.
Rihet P, Traore Y, Abel L, Aucan C, Traore-Leroux T, Fumoux F . Malaria in humans: Plasmodium falciparum blood infection levels are linked to chromosome 5q31–q33. Am J Hum Genet 1998; 63: 498–450.
Traore Y, Rihet P, Traore-Leroux T et al. Analysis of the genetic factors controlling malarial infection in man. Sante 1999; 9: 53–59.
Kruglyak L, Daly MJ, Reeve DM, Lander ES . Parametric and nonparametric linkage analysis: a unified multipoint approach. Am J Hum Genet 1996; 58: 1347–1363.
Garcia A, Marquet S, Bucheton B et al. Linkage analysis of blood Plasmodium falciparum levels: interest of the 5q31–q33 chromosome region. Am J Trop Med Hyg 1998; 58: 705–709.
Marquet S, Abel L, Hillaire D et al. Genetic localization of a locus controlling the intensity of infection by Schistosoma mansoni on chromosome 5q31–q33. Nat Genet 1996; 14: 181–184.
Muller-Myhsok B, Stelma FF, Guisse-Sow F et al. Further evidence suggesting the presence of a locus, on human chromosome 5q31–q33, influencing the intensity of infection with Schistosoma mansoni. Am J Hum Genet 1997; 61: 452–454.
Meyers DA, Postma DS, Panhuysen CI et al. Evidence for a locus regulating total serum IgE levels mapping to chromosome 5. Genomics 1994; 23: 464–470.
Xu J, Postma DS, Howard TD et al. Major genes regulating total serum immunoglobulin E levels in families with asthma. Am J Hum Genet 2000; 67: 1163–1173.
Vignal A, Gyapay G, Hazan J et al. A non-radioactive multiplex procedure for genotyping of microsatellite markers. In: Adolph, K. (ed). Methods in Molecular Genetics 1: Gene and Chromosome Analysis. Academic Press: San Diego, 1993, pp 211–221.
Dib C, Faure S, Fizames C et al. A comprehensive genetic map of the human genome based on 5,264 microsatellites. Nature 1996; 380: 152–154.
Pratt SC, Daly MJ, Kruglyak L . Exact multipoint quantitative-trait linkage analysis in pedigrees by variance components. Am J Hum Genet 2000; 66: 1153–1157.
Lathrop GM, Lalouel JM, Julier C, Ott J . Strategies for multilocus linkage analysis in humans. Proc Natl Acad Sci USA 1984; 81: 3443–3446.
Abecasis GR, Cardon LR, Cookson WO . A general test of association for quantitative traits in nuclear families. Am J Hum Genet 2000; 66: 279–292.
Acknowledgements
This research was supported by the French Ministry of Research and Technology, the Fondation pour la Recherche Médicale (France), the Conseil Régional Provence Alpes Côte d'Azur (France), and the Conseil Général des Bouches du Rhône (France). BK and CA were, respectively, supported by studentships from the Agence Universitaire de la Francophonie and the Fondation pour la Recherche Médicale. LF is supported by a studentship from the French Ministry of Research and Technology.
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Flori, L., Kumulungui, B., Aucan, C. et al. Linkage and association between Plasmodium falciparum blood infection levels and chromosome 5q31–q33. Genes Immun 4, 265–268 (2003). https://doi.org/10.1038/sj.gene.6363960
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DOI: https://doi.org/10.1038/sj.gene.6363960
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