RET and Hirschsprung disease: In some cases, the genetic background effect involves a mutation in a gene already known to be associated with Hirschsprung disease: a human genome-wide association study demonstrated genetic interaction between the EDNRB and RET loci (Carrasquillo et al., 2002), and synergy was evident in mice with intentional combinations of Ednrb and Ret (McCallion et al., 2003) or Ednrb and Sox10 (Cantrell et al., 2004) alleles.