Comparative functional genomic studies require the proper identification of gene 
orthologs to properly exploit animal biomedical research models. To identify 
gene orthologs, comprehensive, conserved gene synteny analyses are necessary to 
unwind gene histories that are convoluted by two rounds of early vertebrate 
genome duplication, and in the case of the teleosts, a third round, the teleost 
genome duplication (TGD). Recently, the genome of the spotted gar, a holostean 
outgroup to the teleosts that did not undergo this third genome duplication, was 
sequenced and applied as an orthology bridge to facilitate the identification of 
teleost orthologs to human genes and to enhance the power of teleosts as 
biomedical models. In this study, we apply the spotted gar orthology bridge to 
help describe the gene history of the vertebrate TNFAIP8 family. Members of the 
TNFAIP8 gene family have been linked to regulation of immune function and 
homeostasis and the development of multiple cancer types. Through a conserved 
gene synteny analysis, we identified zebrafish orthologs to human TNFAIP8L1 and 
TNFAIP8L3 genes and two co-orthologs to human TNFAIP8L2, but failed to identify 
an ortholog to human TNFAIP8. Through the application of the orthology bridge, 
we determined that teleost orthologs to human TNFAIP8 genes were likely lost in 
a genome inversion event after their divergence from their common ancestor with 
spotted gar. These findings demonstrate the value of this enhanced approach to 
gene history analysis and support the development of teleost models to study 
complex questions related to an array of biomedical issues, including immunity 
and cancer.