title: HEREDITARY FACTOR VII DEFICIENCY IN THE ASIAN ELEPHANT (ELEPHAS MAXIMUS) CAUSED BY A F7 MISSENSE MUTATION.
abstract: Hereditary disorders and genetic predispositions to disease are rarely reported in captive and free-ranging wildlife, and none have been definitively identified and characterized in elephants. A wild-caught, 41-yr-old male Asian elephant ( Elephas maximus ) without an apparent increased bleeding tendency was consistently found to have prolonged prothrombin times (PTs, mean=55±35 s) compared to 17 other elephants (PT=10±2 s). This elephant's partial thromboplastin times (PTT) fell within the normal range of the other elephants (12-30 s). A prolonged PT in the presence of a normal PTT suggests disruption of the extrinsic pathway via deficiency of coagulation Factor VII (FVII). This elephant's plasma FVII activity was very low (2%) compared to that of 15 other elephants (57-80%), but other coagulation factors' activities did not differ from the control elephants. Sequencing of genomic DNA from ethylenediaminetetraacetic acid blood revealed a single homozygous point mutation (c.202A>G) in the F7 gene of the FVII deficient elephant that was not present in unrelated elephants. This mutation causes an amino acid substitution (p.Arg68Gly) that is predicted to be deleterious. Two living offspring of the affected elephant were heterozygous for the mutation and had normal plasma FVII activities and coagulation profiles. Tissue from a third offspring, a deceased calf, was utilized to show that it was also a heterozygote. A DNA test has been developed to enable the screening of additional elephants for this mutation. Consistent with FVII deficiency investigations in other species, the condition did not cause a serious bleeding tendency in this individual elephant.
authors.affiliation: 1   Melbourne Zoo, PO Box 74, Parkville VIC 3052, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Lynch
authors.affiliation: 2   Australian Genome Research Facility, Research Road, University of Queensland, St. Lucia, Queensland 4072, Australia.
authors.forename: Ken
authors.initials: K
authors.lastname: McGrath
authors.affiliation: 3   Section of Medical Genetics, School of Veterinary Medicine, University of Pennsylvania, 3900 Delancey Street, Philadelphia, Pennsylvania 19104-6010, USA.
authors.forename: Karthik
authors.initials: K
authors.lastname: Raj
authors.affiliation: 4   Gribbles Veterinary Pathology, 1868 Dandenong Road, Clayton VIC 3168, Australia.
authors.forename: Philippa
authors.initials: P
authors.lastname: McLaren
authors.affiliation: 5   Perth Zoo, 20 Labouchere Road, South Perth, Western Australia 6951, Australia.
authors.forename: Karen
authors.initials: K
authors.lastname: Payne
authors.affiliation: 4   Gribbles Veterinary Pathology, 1868 Dandenong Road, Clayton VIC 3168, Australia.
authors.forename: Richard
authors.initials: R
authors.lastname: McCoy
authors.affiliation: 3   Section of Medical Genetics, School of Veterinary Medicine, University of Pennsylvania, 3900 Delancey Street, Philadelphia, Pennsylvania 19104-6010, USA.
authors.forename: Urs
authors.initials: U
authors.lastname: Giger
mesh_terms: D000818:Animals; D000835:Animals, Wild; D004606:Elephants / Q000235:genetics*; D005168:Factor VII Deficiency / Q000662:veterinary*; D008297:Male; D009154:Mutation; D020125:Mutation, Missense
keywords: Bleeding coagulopathy; blood; elephant; genetic disease