Modeling inheritance of malignant melanoma with DNA markers in Sinclair swine.
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).
Gomez-Raya
L
L
Department of Animal Biotechnology, University of Nevada, Reno, Nevada 89557, USA. lgomezraya@cabnr.unr.edu
Okomo-Adhiambo
M
M
Beattie
C
C
Osborne
K
K
Rink
A
A
Rauw
W M
WM
D000483:Alleles; D000818:Animals; D002874:Chromosome Mapping; D005819:Genetic Markers; D006579:Heterozygote; D006720:Homozygote; D040582:Inheritance Patterns / Q000235:genetics*; D008126:Lod Score; D008545:Melanoma / Q000235:genetics*; D008957:Models, Genetic; D019683:Penetrance; D011995:Recombination, Genetic / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics*; D013552:Swine
D005819:Genetic Markers