Cited research: Proc. Natl Acad. Sci. USA 107, 10602–10607 (2010)

Hundreds of genetic variants are associated with complex diseases, but in most cases little is known about how the variants actually contribute to the disease.

Nicholas Katsanis at Duke University in Durham, North Carolina, and his colleagues have developed a model system using zebrafish (Danio rerio) to tease out such contributions to a rare genetic disorder known as Bardet–Biedl syndrome (BBS). Fourteen human genes have been linked to BBS, which has a range of symptoms, from retinal degeneration to mental retardation.

The researchers systematically replaced the fish versions of BBS genes with some of the 125 known human variants of the genes and observed developing fish embryos. Their technique revealed surprising quirks in the disease's inheritance, including interactions between genes that affect disease severity. The approach could be used to study the genetics of other diseases. B.M.