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Genome-wide scan for visceral leishmaniasis susceptibility genes in Brazil

Genes & Immunity volume 8, pages 84–90 (2007)Cite this article

Abstract

A genome-wide scan was conducted for visceral leishmaniasis (VL) in Brazil. Initially, 405 markers were typed in 22 multicase pedigrees (28 nuclear families; 174 individuals; 66 affected). Non-parametric multipoint analysis detected nine chromosomal regions with provisional evidence (logarithm of the odds (LOD) scores 0.95–1.66; 0.003<P<0.018) for linkage. To confirm linkage, 132 individuals (43 affected) from 19 independently ascertained families were genotyped across these regions. Three regions (6q27, 7q11.22 and 17q11.2–q21.3) retained evidence (LOD scores 1.08, 1.34, 1.14; P=0.013, 0.007, 0.011) for linkage. To determine which genes contribute to linkage at 17q11.2–q21.3, 80 single nucleotide polymorphisms were genotyped in 98 nuclear families with 183 affected individuals. Family-based association test analysis indicated associations at two chemokine genes, CCL1 and CCL16, that lie 1.6 Mb apart, show some extended linkage disequilibrium with each other, but each lie within different clusters of candidate CCL genes. Multiple genes may therefore contribute to the linkage peak for VL at 17q12.

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Acknowledgements

This work was funded by grants from the Wellcome Trust and NIH (NIH/AI30639 to SMJ and Dr Edgar Carvalho). We thank the families from northeastern Brazil for their contribution to this study.

Author information

Author notes

  1. S E Jamieson and E N Miller: These two authors contributed equally to the work.

Authors and Affiliations

  1. Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, UK

    S E Jamieson, E N Miller, C S Peacock, M Fakiola & J M Blackwell

  2. Division of Infectious Diseases,

    M E Wilson & A Bales-Holst

  3. Department of Internal Medicine, Iowa City, IA, USA

    M E Wilson & A Bales-Holst

  4. Department of Biology, University of Leeds, Leeds, UK

    M-A Shaw

  5. Instituto Evandro Chagas, Belem, Para, Brazil

    F Silveira & J J Shaw

  6. Department of Parasitology, Institute of Biomedical Sciences, São Paulo University, São Paulo, Brazil

    J J Shaw

  7. Department of Biochemistry,

    S M Jeronimo

  8. Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil

    S M Jeronimo

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  1. S E Jamieson
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  8. F Silveira
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Corresponding author

Correspondence to J M Blackwell.

Additional information

Electronic Database Information

1. WHO sites for leishmaniasis prevalence including Brazil http://www.who.int/leishmaniasis/en/ and http://www.who.int/leishmaniasis/burden/en/

2. ABI products https://products.appliedbiosystems.com/ab/en/US/adirect/ab

3. Primer3 software (http://frodo.wi.mit.edu/)

4. Stata v8.2 http://www.stata.com/

5. Cambridge Institute for Medical Research – David Clayton software http://www-gene.cimr.cam.ac.uk/clayton/software/

6. FBAT http://www.biostat.harvard.edu/~fbat/default.html

7. HapMap Project Site http://www.hapmap.org/

Supplementary Information accompanies the paper on Genes and Immunity website (http://www.nature.com/gene)

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Jamieson, S., Miller, E., Peacock, C. et al. Genome-wide scan for visceral leishmaniasis susceptibility genes in Brazil. Genes Immun 8, 84–90 (2007). https://doi.org/10.1038/sj.gene.6364357

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