title: Canine polydactyl mutations with heterogeneous origin in the conserved intronic sequence of LMBR1.
abstract: Canine preaxial polydactyly (PPD) in the hind limb is a developmental trait that restores the first digit lost during canine evolution. Using a linkage analysis, we previously demonstrated that the affected gene in a Korean breed is located on canine chromosome 16. The candidate locus was further limited to a linkage disequilibrium (LD) block of <213 kb composing the single gene, LMBR1, by LD mapping with single nucleotide polymorphisms (SNPs) for affected individuals from both Korean and Western breeds. The ZPA regulatory sequence (ZRS) in intron 5 of LMBR1 was implicated in mammalian polydactyly. An analysis of the LD haplotypes around the ZRS for various dog breeds revealed that only a subset is assigned to Western breeds. Furthermore, two distinct affected haplotypes for Asian and Western breeds were found, each containing different single-base changes in the upstream sequence (pZRS) of the ZRS. Unlike the previously characterized cases of PPD identified in the mouse and human ZRS regions, the canine mutations in pZRS lacked the ectopic expression of sonic hedgehog in the anterior limb bud, distinguishing its role in limb development from that of the ZRS.
authors.affiliation: Department of Genetic Engineering, College of Natural Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Kiyun
authors.initials: K
authors.lastname: Park
authors.forename: Joohyun
authors.initials: J
authors.lastname: Kang
authors.forename: Krishna Pd
authors.initials: KP
authors.lastname: Subedi
authors.forename: Ji-Hong
authors.initials: JH
authors.lastname: Ha
authors.forename: Chankyu
authors.initials: C
authors.lastname: Park
mesh_terms: D000818:Animals; D001483:Base Sequence; D017124:Conserved Sequence; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs; D006239:Haplotypes; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D007438:Introns; D015810:Linkage Disequilibrium; D008565:Membrane Proteins / Q000235:genetics*; D018895:Microsatellite Repeats; D008957:Models, Genetic; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D017689:Polydactyly / Q000235:genetics / Q000662:veterinary*; D020641:Polymorphism, Single Nucleotide
chemical_list: D053823:Hedgehog Proteins; D008565:Membrane Proteins