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United States Department of Agriculture

Agricultural Research Service

Title: Identifying Tumor Initiator/suppressor and Penetrance-Associated Genes by Gene Mapping

Authors
item Smith, Timothy
item Beattie, Craig

Submitted to: International Symposium: Swine And Biomedical Research
Publication Type: Proceedings
Publication Acceptance Date: October 15, 1995
Publication Date: N/A

Interpretive Summary: The genetic linkage map of the porcine genome has become sufficiently developed to allow the mapping of a variety of genes affecting traits of interest. To map such a gene, the genetic markers that make up the map are tested on animal pedigrees that show variation in the trait of interest, for example in a herd having animals that inherit melanoma (a disease commonly seen in Sinclair miniature swine). If the inheritance of a particular marker is commonly associated with the presence of melanoma, then it is likely that a gene involved in the inheritance of the disease lies somewhere on the chromosome near that marker. As a model system, we have helped to set up a breeding program to map a major gene involved in the inheritance of malignant melanoma in a herd of miniature swine being bred at Texas A&M University. We discuss the theoretical considerations in setting up a mapping population, and the use of the information obtained from the mapping experiment to ultimately identify the gene affecting the trait. These considerations are generally applicable to mapping genes affecting any attributes of swine that are heritable, including genes affecting agriculturally important traits as well as the inheritance of disease susceptibility in swine models for human disorders.

Technical Abstract: The genetic linkage map of swine has undergone a dramatic advancement during the last three years. A linkage map containing more than 1000 polymorphic markers is currently available. The vast majority of markers are microsatellites, which are both highly polymorphic and easily genotypable, making it feasible to map genes affecting disease in defined populations of swine. In many regions of the genome, marker density and map resolution are sufficient to permit positional and/or positional candidate cloning. Thus, the power of genetic mapping can now be used to identify loci affecting the inheritance and penetrance of disease-related traits. We have initiated mapping of tumor initiator/suppressor loci, and factors influencing disease penetrance, in a herd of miniature swine that exhibit a heritable form of malignant melanoma (Sinclair Swine Cutaneous Melanoma, SSCM). Pedigree analysis has demonstrated the existence of a major dominant gene responsible for the inheritance of the disease, and the location of a major penetrance factor in or near the SLA. This analysis has predicted genotypes of individual animals based on their pedigree, allowing us to make mating choices to maximize the probability of successfully mapping these loci.

Last Modified: 10/24/2014
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