Genetics, Vol. 176, 585-597, May 2007, Copyright © 2007
doi:10.1534/genetics.106.070268

Modeling Inheritance of Malignant Melanoma With DNA Markers in Sinclair Swine

L. Gomez-Raya1, M. Okomo-Adhiambo, C. Beattie2, K. Osborne, A. Rink and W. M. Rauw

Department of Animal Biotechnology, University of Nevada, Reno, Nevada 89557

1 Corresponding author: Department of Animal Biotechnology, University of Nevada, Mail Stop 202, Reno, NV 89557.
E-mail: lgomezraya{at}cabnr.unr.edu

Cutaneous malignant melanoma in Sinclair swine is a hereditary disease that develops in utero or during the first 6 weeks of life. In many cases, the tumors regress and piglets survive the disease. Two different sets of gene(s) might be involved in the disease: tumor initiator (suppressor) locus or loci and loci affecting the aggressiveness of the disease (number and stage of tumors). We develop maximum-likelihood methods for interval mapping for both types of loci. The experimental design consisted of a boar mated to tumor-bearing sows with recording of tumor status and number of tumors in the 6 weeks of life of the offspring. The model to search for the tumor initiator locus (with alleles T and t) was tested by computer simulation. Estimates of penetrances ({Psi}TT and {Psi}Tt for genotypes TT and Tt, respectively) were accurate even for small family sizes. Statistical power was >99% for a family size of 70 with {Psi}TT = 1 and {Psi}Tt = 0. The models to test for number of tumors incorporated genotype information for the tumor initiator locus. All models were tested with data from a single boar family of 72 piglets over swine chromosomes 6 and 8 (SSC6 and SSC8). No tumor evidence for initiator loci was found associated with these chromosomes. However, association of a QTL affecting number of tumors at birth near microsatellite SW1953 on SSC8 was chromosomewise significant (P < 0.0124).