SHORT COMMUNICATION doi:10.1111/j.1365-2052.2011.02203.x Polymorphisms of the SLC11A1 gene and resistance to bovine tuberculosis in African Zebu cattle H. N. Kadarmideen* ,† , A. A. Ali †,‡ , P. C. Thomson ‡ , B. Mu ¨ ller § and J. Zinsstag ¶ *Division of Genetics and Bioinformatics, Department of Animal and Veterinary Basic Sciences, Faculty of Life Sciences, University of Copenhagen, 1870 Frederiksberg C, Copenhagen, Denmark. † CSIRO Livestock Industries, ATSIP, James Cook University Campus, PMB PO Aitkenvale, Townsville QLD 4814, Australia. ‡ University of Sydney, Private Bag 4003, Narellan NSW 2567, Australia. § Faculty of Health Sciences, Stellenbosch University, Cape Town, South Africa. ¶ Department of Public Health and Epidemiology, Swiss Tropical Institute, Basel, CH 4002, Switzerland Summary Bovine tuberculosis (BTB) is a considerable health threat to livestock keepers and general communities in many developing countries. Information on genetic resistance or suscep- tibility because of polymorphisms of candidate genes could be used in making selection decisions for breeding disease tolerant/resistant animals. Here, we investigated associations between polymorphisms at the solute carrier family 11 (proton-coupled divalent metal ion transporters), member 1 gene (SLC11A1, previously known as natural resistant associated macrophage protein 1, NRAMP1), with BTB phenotypes in Chadian cattle. Phenotypes were (i) single intradermal comparative cervical tuberculin test (SICCT) outcome, (ii) presence of gross visible lung lesions, (iii) a bacteriological culture test outcome and (iv) a predicted true BTB infection status using a Bayesian model. All traits were recorded as binary (presence or absence) traits. A total of 211 cattle were genotyped for a microsatellite within the SLC11A1 candidate gene. Standard linear and threshold-liability models regressing BTB traits on copy number of SLC11A1 alleles revealed statistically significant effects of SLC11A1 alleles (P < 0.001) on most BTB traits. Polymorphisms (alleles 211, 215 and 217) are significantly related to lower incidence of BTB traits in Chadian cattle. This is the first study to report the association of SLC11A1 gene polymorphisms with BTB traits in Chadian or any other African cattle breeds. Keywords association, bovine tuberculosis, Mycobacterium bovis, SLC11A1 polymorphism. Mycobacterium bovis causes bovine tuberculosis (BTB), an important disease of domesticated cattle that has a major economic and health impact, including human deaths through zoonosis. Polymorphisms within candidate genes have been shown to affect phenotypic outcomes in many economically important traits and clinical diseases in ani- mals (e.g. Kadarmideen 2008); this information could be used in making selection decisions for breeding disease tol- erant/resistant animals. With this as motivation, we investigated the solute carrier family 11 (proton-coupled divalent metal ion transporters), member 1 gene (SLC11A1, previously known as natural resistant associated macrophage protein 1, NRAMP1), a known candidate gene associated with natural resistance to infection by Mycobaterium spp in cattle (Barthel et al. 2000). The SLC11A1 gene mediates activity of macrophages against intracellular parasites during the early stages of infection. We investigated polymorphisms of the SLC11A1 gene and their association with the following four phenotypes: (i) single intra-dermal comparative cervical tuberculin test (SICCT) outcome, (ii) presence of visible lung lesions, (iii) a bacteriological culture test outcome and (iv) predicted true BTB infection by a Bayesian model (BM). A total of 251 animals from Mbororo (87) and Arab (164) breeds were sampled during 2005 at abattoirs in Southern Chad (see Fig. 1a, b). Details of the resource population have been described previously (Ngandolo et al. 2009). The SICCT, performed on live animals (details in Mu ¨ ller et al. 2009), was recorded as 1 if skin thickness >4 mm or 0 if skin thickness £4 mm. After slaughter, all cattle carcasses were subjected to inspection by trained local veterinary officers for the presence of gross visible lung lesions indicative of Address for correspondence Haja Kadarmideen, Division of Genetics and Bioinformatics, Depart- ment of Animal and Veterinary Basic Sciences, Faculty of Life Sciences, University of Copenhagen, Groennegaardsvej 3, 1870 Frederiksberg C, Denmark. E-mail: hajak@life.ku.dk Accepted for publication 24 January 2011 Ó 2011 The Authors, Animal Genetics Ó 2011 Stichting International Foundation for Animal Genetics, 42, 656–658 656