Whole-Genome Sequencing Confirms Avian Model of Human Disease
For more than 60 years, developmental biologists have studied a naturally occurring avian mutant called talpid2 because of its interesting phenotypes, including cleft lip/palate, oral dysmorphologies and limb defects. However, the talpid2 has been of limited utility because researchers did not know what caused the mutation – until now.
The solution came from the lab of Samantha Brugmann, PhD, which cracked the genetic, molecular and cellular code on how and why the talpid2 mutation occurs. Their findings appeared in the August 2014 issue of Development.
Using whole-genome sequencing, a group of researchers from Cincinnati Children’s and four other universities traced the talpid2 mutation to a ciliary gene called C2CD3, which causes a significant reduction in the number of cells that extend a primary cilium. The team also identified molecular disruptions that occur in the Hedgehog (Hh) signaling pathway, leading to the facial and limb abnormalities associated with talpid2.
“Recently, the study of primary cilia has exploded because of the identification of a large class of human diseases called ciliopathies,” Brugmann says. “Now that we know what gene causes this defect in chickens – as well as the molecular and cellular pathway that is involved — we have an avian model for human disease.”
An accompanying Development editorial, titled “talpid2: A Mystery Finally Solved,” states: “Identification of the talpid2 locus has been long awaited, and although there is still much to understand about how C2CD3 regulates cilia formation and function, and SHH signaling, these data provide an important step in this direction.”
This prediction has come to fruition as the group, in a subsequent publication (Schock et al., 2015 in Disease Models & Mechanisms), has shown that talpid2 is a bona fide model for the human ciliopathy called oral-facial-digital syndrome.
