Radiation hybrid mapping of cataract genes in the dog

[摘要] Purpose: To facilitate the molecular characterization of naturallyoccurring cataracts in dogs by providing the radiation hybrid locationof 21 cataract-associated genes along with their closely associatedpolymorphic markers. These can be used for segregation testing of thecandidate genes in canine cataract pedigrees.Methods: Twenty-one genes with known mutations causing hereditarycataracts in man and/or mouse were selected and mapped to caninechromosomes using a canine:hamster radiation hybrid RH5000 panel. Eachcataract gene ortholog was mapped in relation to over 3,000 markersincluding microsatellites, ESTs, genes, and BAC clones. The resultingindependently determined RH-map locations were compared with thecorresponding gene locations from the draft sequence of the caninegenome.Results: Twenty-one cataract orthologs were mapped to caninechromosomes. The genetic locations and nearest polymorphic markers weredetermined for 20 of these orthologs. In addition, the resultingcataract gene locations, as determined experimentally by this study,were compared with those determined by the canine genome project. Allgenes mapped within or near chromosomal locations with previouslyestablished homology to the corresponding human gene locations based oncanine:human chromosomal synteny.Conclusions: The location of selected cataract gene orthologs in thedog, along with their nearest polymorphic markers, serves as a resourcefor association and linkage testing in canine pedigrees segregatinginherited cataracts. The recent development of canine genomic resourcesmake canine models a practical and valuable resource for the study ofhuman hereditary cataracts. Canine models can serve as large animalmodels intermediate between mouse and man for both gene discovery andthe development of novel cataract therapies.

[学科分类] 生物化学/生物物理