One of the most significant obstacles to harvesting insight from sequence analyses is our limited ability to test whether potentially causal sequence variants are likely to have functional consequences. As demonstrated repeatedly, the extensive conservation of gene function across vertebrate species means expression of human alleles in zebrafish embryos lacking a gene function can be used to distinguish wildtype from loss-of-function human alleles.
We use the zebrafish for rapidly testing the functionality of candidate variant alleles suspected of contributing to osteoarthritis and other bone and joint abnormalities. Our studies indicate that gain- and loss-of-function assays in the zebrafish efficiently detect whether variant alleles discovered in the family studies have functional consequences.
Furthermore, by analyzing gene function in zebrafish we can gain insight in to the pathways and biological processes that contribute to the onset and progression of disease processes.