A genome-wide linkage scan in German shepherd dogs localizes canine platelet procoagulant deficiency (Scott syndrome) to canine chromosome 27.
Scott syndrome is a rare hereditary bleeding disorder associated with an inability of stimulated platelets to externalize the negatively charged phospholipid, phosphatidylserine (PS). Canine Scott syndrome (CSS) is the only naturally occurring animal model of this defect and therefore represents a unique tool to discover a disease gene capable of producing this platelet phenotype. We undertook platelet function studies and linkage analyses in a pedigree of CSS-affected German shepherd dogs. Based on residual serum prothrombin and flow cytometric assays, CSS segregates as an autosomal recessive trait. An initial genome scan, performed by genotyping 48 dogs for 280 microsatellite markers, suggested linkage with markers on chromosome 27. Genotypes ultimately obtained for a total of 56 dogs at 11 markers on chromosome 27 revealed significant LOD scores for 2 markers near the centromere, with multipoint linkage indicating a CSS trait locus spanning approximately 14 cm. These results provide the basis for fine mapping studies to narrow the disease interval and target the evaluation of putative disease genes.
Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA. mbb9@cornell.edu
Marjory
M
Brooks
Krystal
K
Etter
James
J
Catalfamo
Abra
A
Brisbin
Carlos
C
Bustamante
Jason
J
Mezey
D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D033481:Chromosomes, Mammalian / Q000235:genetics*; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006470:Hemorrhage / Q000235:genetics / Q000662:veterinary*; D006801:Humans; D008126:Lod Score; D008297:Male; D010375:Pedigree; D011517:Prothrombin Time; D013577:Syndrome
D005819:Genetic Markers