Abstract
Small ruminant lentiviruses (SRLVs) are a heterogeneous group of viruses of sheep, goat, and wild ruminants responsible of lifelong persistent infection leading to a multisystem chronic disease. Increased evidences indicate that host genetic factors could influence the individual SRLV resistance. The present study was conducted on the Garfagnina goat breed, an Italian goat population registered on the Tuscan regional repertory of genetic resources at risk of extinction. Forty-eight adult goats belonging to a single flock were studied. SRLV diagnosis was achieved by serological tests and 21 serologically positive animals were identified. All animals were genotyped with the Illumina GoatSNP60 BeadChip and a genome-wide scan was then performed on the individual marker genotypes, in an attempt to identify genomic regions associated with the infection. One SNP was found significant (P < 5 × 10−5) on CHR 18 at 62,360,918 bp. The SNP was an intron of the zinc finger protein 331 (ZNF331) protein. In the region 1 Mb upstream the significant SNP, the NLRP12 (NLR family pyrin domain containing 12), the PRKCG (protein kinase C gamma), and the CACNG7 (calcium voltage-gated channel auxiliary subunit gamma 7) were found.


References
Amin, N., van Duijn CM, Y.S. Aulchenko. 2007. A genomic background based method for association analysis in related individuals. PloS One 2:1274.
Borte, S., Celiksoy, M.H., Menzel, V., Ozkaya, O., Ozen, F.Z., Hammarström, L. and Yildiran, A., 2014.Novel NLRP12 mutations associated with intestinal amyloidosis in a patient diagnosed with common variable immunodeficiency. Clinical Immunology, 154, 105–111.
Burton, P.R., Clayton, D.G., Cardon, L.R., Craddock, N., Deloukas, P., Duncanson, A., Kwiatkowski, D.P., McCarthy, M.I.,. Ouwehand, W.H. and Samani, N.J., 2007. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature, 447, 661–678.
Cecchi, F., Russo, C., Iamartino, D., Galiero, A., Turchi, B., Fratini, F., Degl’Innocenti, S., Mazza, R., Biffani, S., Preziuso, G. and Cantile, C., 2017. Identification of candidate genes for paratuberculosis resistance in the native Italian Garfagnina goat breed. Tropical Animal Health and Production, 49, 1135–1142.
Cecchi, F., Fratini, F., Bandecchi, P., Cantile, C. and Mazzei, M., 2018. Investigation on goat lentiviral infections and preliminary association analysis with microsatellites in the native Garfagnina goats breed. Rendiconti Lincei. Scienze Fisiche e Naturali, in press, https://doi.org/10.1007/s12210-018-0729-0
Chen, W.-M. and Abecasis, G.R,2007. Family-Based Association Tests for Genomewide Association Scans. American Journal of Human Genetics, 81, 913–926.
Chen, R.S., Deng, T.C., Garcia, T., Sellers, Z.M. and Best, P.M., 2007. Calcium channel gamma subunits: a functionally diverse protein family. Cell Biochemistry and Biophysics, 47, 178–186.
Clawson, M.L., Redden, R., Schuller, G., Heaton, M.P., Workman, A., Chitko-McKown, C.G., Smith, T.P. and Leymaster, K.A., 2015. Genetic subgroup of small ruminant lentiviruses that infects sheep homozygous for TMEM154 frameshift deletion mutation A4Δ53. Veterinary Research, 46, 22.
Clements, J.E. and Narayan, O., 1989. Biology and pathogenesis of lentiviruses. Journal of General Virology, 70, 1617–39.
GenABEL project developers. 2013. GenABEL: Genome-wide SNP association analysis. .R package version 1.8-0: http://CRAN.R-project.org/package=GenABEL.
Heaton, M.P., Clawson, M.L., Chitko-McKown, C.G., Leymaster, K.A., Smith, T.P., et al. 2012. Reduced Lentivirus Susceptibility in Sheep with TMEM154 Mutations. PLoS Genet 8: e1002467.
Ji, J. Hassler, M.L., Shimobayashi, E., Paka, N., Streit, R. and Kapfhammer, J.P., 2014. Increased protein kinase C gamma activity induces Purkinje cell pathology in a mouse model of spinocerebellar ataxia 14. Neurobiology Disease, 70, 1–11.
Larruskain, A. and Begoña, J.M., 2013. Retroviral Infections in Sheep and Goats: Small Ruminant Lentiviruses and Host Interaction. Viruses, 8, 2043–2061
Larruskain, A., Minguijón, E., García-Etxebarria, K., Moreno, B., Arostegui, I., Juste, R.A. and Jugo, B.M., 2010. MHC class II DRB1 gene polymorphism in the pathogenesis of Maedi-Visna and pulmonary adenocarcinoma viral diseases in sheep. Immunogenetics, 62(2), 75–83
Peterhans, E., Geenland, T., Badiola, J., Harkiss, G., Bertoni, G., Amorena, B., et al. 2004. Routes of transmission and consequences of small ruminant lentiviruses (SRLVs) Infection and eradication schemes. Veterinary Research, 35, 257–74.
Petursson, G., Nathansson, N., Georgsson, G., Panitch, H. and Palsson P.A., 1976. Pathogenesis of Visna. I. Sequential virologic, serologic, and pathologic studies. Laboratory Investigation, 35, 402–12.
R Core Team. 2013. R: A language and environment for statistical computing. http://www.R-project.org/.
Sider, LH., Heaton, M.P., Chitko-McKown, C.G., Harhay, G.P., Smith, T.P.L., Leymaster, K.A., Laegreid, W.W. and Clawson, M.L. 2013. Small ruminant lentivirus genetic subgroups associate with sheep TMEM154 genotypes. Veterinary Research, 44, 64.
Turner, S.D. 2014. qqman: an R package for visualizing GWAS results using QQ and manhattan plots. bioRxiv 005165.
Wang, W., Ye, C., Di Zhang, J.L., Kimata, J.T. and Zhou, P., 2014. CCR5 Gene Disruption via Lentiviral Vectors Expressing Cas9 and Single Guided RNA Renders Cells Resistant to HIV-1 Infection PLOS Published: December 26, 2014 https://doi.org/10.1371/journal.pone.0115987
White, S.N, Mousel, M.R., Herrmann-Hoesing, L.M., Reynolds, J.O., Leymaster, K.A., et al. 2012. Genome-Wide Association Identifies Multiple Genomic Regions Associated with Susceptibility to and Control of Ovine Lentivirus. PLoS ONE 7: e47829.
Yu, J., Liang, Q.Y., Wang, J., Y Cheng, Y., Wang, S., Poon, T.C., Go, M.Y., Tao, Q., Z Chang, Z., Sung, J.J., 2013. Zinc-finger protein 331, a novel putative tumor suppressor, suppresses growth and invasiveness of gastric cancer. Oncogene, 32, 307–317.
Zanoni, R.G., 1998. Phylogenetic analysis of small ruminant lentiviruses. J. Gen. Journal of General Virology, 79, 1951–1961.
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This work was supported by grants of the University of Pisa (PRA 2016).
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Committee on the Ethics of Animal Experiments of Minimally Invasive Surgery Centre (Italian laws).
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Cecchi, F., Dadousis, C., Bozzi, R. et al. Genome scan for the possibility of identifying candidate resistance genes for goat lentiviral infections in the Italian Garfagnina goat breed. Trop Anim Health Prod 51, 729–733 (2019). https://doi.org/10.1007/s11250-018-1728-y
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DOI: https://doi.org/10.1007/s11250-018-1728-y