Radiation hybrid mapping of cataract genes in the dog.
OBJECTIVE
To facilitate the molecular characterization of naturally occurring cataracts in dogs by providing the radiation hybrid location of 21 cataract-associated genes along with their closely associated polymorphic markers. These can be used for segregation testing of the candidate genes in canine cataract pedigrees.


METHODS
Twenty-one genes with known mutations causing hereditary cataracts in man and/or mouse were selected and mapped to canine chromosomes using a canine:hamster radiation hybrid RH5000 panel. Each cataract gene ortholog was mapped in relation to over 3,000 markers including microsatellites, ESTs, genes, and BAC clones. The resulting independently determined RH-map locations were compared with the corresponding gene locations from the draft sequence of the canine genome.


RESULTS
Twenty-one cataract orthologs were mapped to canine chromosomes. The genetic locations and nearest polymorphic markers were determined for 20 of these orthologs. In addition, the resulting cataract gene locations, as determined experimentally by this study, were compared with those determined by the canine genome project. All genes mapped within or near chromosomal locations with previously established homology to the corresponding human gene locations based on canine:human chromosomal synteny.


CONCLUSIONS
The location of selected cataract gene orthologs in the dog, along with their nearest polymorphic markers, serves as a resource for association and linkage testing in canine pedigrees segregating inherited cataracts. The recent development of canine genomic resources make canine models a practical and valuable resource for the study of human hereditary cataracts. Canine models can serve as large animal models intermediate between mouse and man for both gene discovery and the development of novel cataract therapies.
Hunter
Linda S
LS
J. A. Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA. lsh22@cornell.edu
Sidjanin
Duska J
DJ
Johnson
Jennifer L
JL
Zangerl
Barbara
B
Galibert
Francis
F
Andre
Catherine
C
Kirkness
Ewen
E
Talamas
Elijah
E
Acland
Gregory M
GM
Aguirre
Gustavo D
GD
D000818:Animals; D002386:Cataract / Q000235:genetics; D002460:Cell Line; D006224:Cricetinae; D004285:Dogs / Q000235:genetics*; D008040:Genetic Linkage; D005819:Genetic Markers; D008126:Lod Score; D011110:Polymorphism, Genetic; D021101:Radiation Hybrid Mapping; D016324:Sequence Tagged Sites
D005819:Genetic Markers