Originally published as Genetics Published Articles Ahead of Print on August 9, 2008.

Genetics, Vol. 179, 2163-2172, August 2008, Copyright © 2008
doi:10.1534/genetics.108.087114

Canine Polydactyl Mutations With Heterogeneous Origin in the Conserved Intronic Sequence of LMBR1

Kiyun Park*, Joohyun Kang*, Krishna Pd. Subedi*, Ji-Hong Ha{dagger} and Chankyu Park*,1

* Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejon 305-701, Republic of Korea and {dagger} Department of Genetic Engineering, College of Natural Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea

1 Corresponding author: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Yuseong-gu, Daejon 305-701, Republic of Korea.
E-mail: ckpark{at}kaist.ac.kr

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.