Scottish Fold cat trait research also targeting human bone defect

During the 23rd annual International Conference on the Status of Plant and Animal Genome Research which was held Jan. 10-14 in San Diego, University of Missouri researcher Barbara Gandolfi noted that the trait which gives Scottish Fold cats their curved ear characteristics is also responsible for bone deformities in humans.

Gandolfi's presentation given during the Jan. 11 Cat and Dog Workshop session of the PAG XXIII conference was titled "Inherited Osteoarthropathy in Scottish Fold Cats is Associated with Altered Calcium Channel Function." The work also involved contributing research from Leslie Lyons, Badri Adhikari, and Jianlin Cheng of the University of Missouri; Richard Malik, Claire Wade, and Bianca Haase of the University of Sydney in Australia; and Shireen Lamande of The Royal Children's Hospital in Australia.

"We have clinical evidence that the breed is affected by osteochondrodysplasia," Gandolfi said.

(Osteochondrodysplasia is associated with abnormal bone and cartilage in a body and has different degrees of severity.)

The Scottish Fold breed, which is part of the Persian cat family, originated in Scotland in the early 1960s. Scottish Fold cats are characterized by their folded ears and, according to clinical, radiologic, histologic, and genetic evidence, Scottish Fold cats have an underlying congenital defect which affects the structure and function of cartilage and results in progressive bone, joint, and cartilage abnormalities which lead to progressive dysfunction.

In humans, inherited osteoarthropathy is characterized by arthropathy of fingers and toes and shortening of the phalanges, and humans who appear normal at birth have severe arthropathy by adulthood.

In Scottish Fold cats, the signs of osteochondrodysplasia appear three to four weeks after birth. "Homozygous cats actually develop crippling arthritis," Gandolfi said.

(A gene has one allele from each parent; if the two alleles are identical the gene is homozygous and if the two alleles differ the gene is heterozygous. A gene is autosomal dominant if only one allele is needed for the phenotype, or observable trait, to occur and is autosomal recessive if both alleles must have that trait for it to be present.)

Pedigree analysis and breeding experiments indicate that the phenotype is inherited as an autosomal dominant trait. Cats with two copies of the mutated gene have a severe phenotype from an early age while heterozygote cats have symptoms whose clinical progression varies in severity from mild to moderate.

A genome-wide association study was performed using 35 cases and 32 controls. The trait was localized to cat chromosome D3, and candidate gene screening identified a gene which is involved in osteoarthropathy, cartilage homeostasis, and skeletal dysplasia in humans. The gene analysis revealed a mutation within a calcium channel associated with the aesthetic and clinical phenotypes.

"We still don't know why there are so many different degrees of severity," Gandolfi said.