Genetic analysis of immune loci in rainbow trout (Oncorhynchus mykiss)

Natural killer cells (NK) are one of the main effectors of the mammalian innate immune response. Lower vertebrates contain functionally equivalent NK-like cells which are often referred to as nonspecific cytotoxic cells (NCC). As such, fish NCC are presumed to protect against bacteria, parasites, viruses and tumor growth. Despite their probable importance to innate immunity and disease resistance, little is known concerning the genetics underlying NCC activity in lower vertebrates. We have propagated two clonal lines of rainbow trout that differ in phenotypic expression of NCC activity. Our clonal line designated HC exhibits higher levels of NCC activity when compared to a clonal line referred to as OSU. These HC and OSU clonal lines provide an attractive resource for investigating the genetics of natural killer cell-like activity in a lower vertebrate model. In this dissertation, we demonstrate NCC activity differences between the OSU and HC lines to be controlled by a single major quantitative trait loci (QTL). This QTL was identified within an OSUxHC doubled haploid population created from an F1 hybrid of the OSU and HC clonal lines. Utilizing genetic mapping, the NCC QTL was shown to be unlinked with MHC I, MHC II, NKEF genes in rainbow trout. Collectively, these results provide a major step toward understanding NCC activity in a lower vertebrate model and provide information concerning the chromosomal associations of functionally important immune related genes in rainbow trout. These results also suggest a region analogous to the natural killer gene complex identified on syntenic portions of mouse chromosome 6, human chromosome 12 and rat chromosome 4 may exist in rainbow trout.; Also in this dissertation, an experimental study concerning the genetic analysis of pyloric caeca development in rainbow trout is reported. Utilizing the OSUxHC genetic map, three QTL associated with pyloric caeca number were identified. Discerning the genetic framework of this phenotype has relevance to aquaculture as increased caeca numbers have been correlated with improved feed efficiencies. In total, the results presented herein demonstrate the utility of clonal rainbow trout lines to facilitate the genetic analysis of complex phenotypes in a commercially important species.