Web of Science: 23 cites, Scopus: 24 cites, Google Scholar: cites,
Genetic control of canine leishmaniasis : genome-wide association study and genomic selection analysis
Quilez Oliete, Javier (Centre de Recerca en Agrigenòmica)
Martínez Díaz, Verónica (Centre de Recerca en Agrigenòmica)
Woolliams, John A. (University of Edinburgh (Easter Bush, Regne Unit). The Roslin Institute)
Sánchez Bonastre, Armando (Centre de Recerca en Agrigenòmica)
Pong-Wong, Ricardo (University of Edinburgh (Easter Bush, Regne Unit). The Roslin Institute)
Kennedy, Lorna J. (University of Manchester (Manchester, Regne Unit). Centre for Integrated Genomic Medical Research)
Quinnell, Rupert J. (University of Leeds (Leeds, Regne Unit). Institute of Integrative and Comparative Biology)
Ollier, William E. R. (University of Manchester (Manchester, Regne Unit). Centre for Integrated Genomic Medical Research)
Roura, Xavier (Universitat Autònoma de Barcelona. Hospital Clínic Veterinari)
Ferrer i Caubet, Lluís (Universitat Autònoma de Barcelona. Hospital Clínic Veterinari)
Altet Sanahujes, Laura (Universitat Autònoma de Barcelona. Departament de Ciència Animal i dels Aliments)
Francino Martí, Olga (Universitat Autònoma de Barcelona. Departament de Ciència Animal i dels Aliments)

Data: 2012
Resum: Background: the current disease model for leishmaniasis suggests that only a proportion of infected individuals develop clinical disease, while others are asymptomatically infected due to immune control of infection. The factors that determine whether individuals progress to clinical disease following Leishmania infection are unclear, although previous studies suggest a role for host genetics. Our hypothesis was that canine leishmaniasis is a complex disease with multiple loci responsible for the progression of the disease from Leishmania infection. Methodology/Principal Findings: genome-wide association and genomic selection approaches were applied to a population-based case-control dataset of 219 dogs from a single breed (Boxer) genotyped for ~170,000 SNPs. Firstly, we aimed to identify individual disease loci; secondly, we quantified the genetic component of the observed phenotypic variance; and thirdly, we tested whether genome-wide SNP data could accurately predict the disease. Conclusions/Significance: we estimated that a substantial proportion of the genome is affecting the trait and that its heritability could be as high as 60%. Using the genome-wide association approach, the strongest associations were on chromosomes 1, 4 and 20, although none of these were statistically significant at a genome-wide level and after correcting for genetic stratification and lifestyle. Amongst these associations, chromosome 4: 61. 2-76. 9 Mb maps to a locus that has previously been associated with host susceptibility to human and murine leishmaniasis, and genomic selection estimated markers in this region to have the greatest effect on the phenotype. We therefore propose these regions as candidates for replication studies. An important finding of this study was the significant predictive value from using the genomic information. We found that the phenotype could be predicted with an accuracy of ~0. 29 in new samples and that the affection status was correctly predicted in 60% of dogs, significantly higher than expected by chance, and with satisfactory sensitivity-specificity values (AUC = 0. 63).
Ajuts: European Commission 201370
Ministerio de Ciencia e Innovación CSD2007-00036
Drets: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Llengua: Anglès
Document: Article ; Versió publicada
Matèria: Leishmaniosi ; Genètica veterinària ; Gossos ; Perros ; Canine leishmaniasis ; Dogs
Publicat a: PloS one, Vol. 7, Issue 4 (April 2012) , p. e35349, ISSN 1932-6203

DOI: 10.1371/journal.pone.0035349
PMID: 22558142

10 p, 253.1 KB

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