Allelic imbalance of Shh expression and polydactyly are linked to a SNP in the ZRS region of Lmbr1 in Silkie chickens

The Silkie chicken breed exhibits dominant preaxial polydactyly in the leg and associated ectopic Shh expression during development. Using a White leghorn/Silkie cross we identified a QTL highly associated with polydactyly and have mapped this locus to a SNP within the 'ZRS' region of intron 5 in Lmbr1, a known limb specific cis-regulatory element which controls expression of Shh in other species (Lettice et al., 2002). We have found that expression of Shh is abnormal in both the anterior and the posterior of the developing Silkie leg; expression is stronger, prolonged and there is allelic imbalance in expression of Shh from Silkie and White leghorn Shh alleles. Limb manipulation experiments provide evidence that the abnormal regulation of posterior Shh expression plays a role in the formation of preaxial polydactyly although ultimately polydactyly is dependent on anterior tissue containing the Silkie ZRS SNP.