Eugenic selection assisted by a BoLA-DR/DQ haplotype associated with susceptibility to bovine dermatophilosis

Dermatophilosis is a severe skin infection of tropical ruminants inducing a loss in productivity and a 15% mortality rate. This disease is due to the actinocyces Dermatophilus congolensis associated with the tick Amblyomma variegatum. Currently, no vaccine is expected and chemoresistance phenomena decrease the means of control (acaricides and antibiotics). Breeders observed that the disease seemed to be controlled by genetic determinism. Based on an 8 year-Iong ecopathological survey of 568 zebu Brahman cattle from several herds located in Martinique Island (FWI), we classified into two extreme groups 123 unrelated animals of both sexes, reared in the same environmental conditions. The most resistant individuals (n=61) were never infected whereas the susceptible individuals (n=62) showed severe clinical signs and later died. Using a functional candidate gene approach we studied the DNA polymorphisms of several targeted genes (macrophage lysosyme, Nramp1, TNF alpha, lymphotoxin, MHC class I and class II molecules (BoLA-DRB3 and DQB) and TcR-CD3) encoding molecules implicated in known mechanisms of both non-specific and specific immune responses. The most significant results were obtained within the Major Histocompatibility Complex (MHC) where the BoLA-DRB3 and DQB genes encode molecules involved in the pathogen/host interface mechanisms, particularly in the antigen presentation to T cell receptors. Firstly in the highly polymorphic BoLA-DRB3 exon 2 encoding the antigen binding groove, we found a particular CESFLQKN amino, acids sequence present in the 5 official alleles DRB3.2*0301, *0302, *0901, *0902, and *1202, which correlates with the susceptibility. On the other hand, we found another strong correlation between susceptibility and the BoLA-DQB*1804 allele. Finally, the most interesting observation is the strong linkage of both previous DRB3.2 and DQB alleles in a unique particular BoLA class II haplotype, which constitutes a highly significant marker (P