title: Cutaneous malignant melanoma and familial dysplastic nevi: evidence for autosomal dominance and pleiotropy.
abstract: Segregation of familial cutaneous melanoma has been shown to be compatible with autosomal dominant transmission with incomplete penetrance. However, the combined phenotype of melanoma and a known melanoma-precursor lesion, the dysplastic nevus (DN), has not previously been found to fit a Mendelian model of inheritance using complex segregation analysis. Employing a life-table and disease-free survival analysis approach, we estimated the lifetime incidence of melanoma in the sibs and offspring of DN-affected individuals to be 46%, consistent with a highly penetrant, autosomal dominant mode of inheritance. To further elucidate the relationship between the two traits, we conducted a linkage analysis between the melanoma locus and a hypothetical DN locus, and obtained a maximum lod score of 3.857 at theta = .08. Furthermore, all families giving evidence for linkage were in the coupling phase and the maximum likelihood estimate of theta was not significantly different from 0 (P = .1). This provides evidence that the DN and melanoma traits may represent pleiotropic effects of a single, highly penetrant gene behaving in an autosomal dominant manner.
authors.forename: S J
authors.initials: SJ
authors.lastname: Bale
authors.forename: A
authors.initials: A
authors.lastname: Chakravarti
authors.forename: M H
authors.initials: MH
authors.lastname: Greene
mesh_terms: D004198:Disease Susceptibility; D005799:Genes, Dominant; D008040:Genetic Linkage; D005819:Genetic Markers; D008545:Melanoma / Q000235:genetics*; D009506:Nevus / Q000235:genetics* / Q000473:pathology; D011230:Precancerous Conditions / Q000235:genetics* / Q000473:pathology; D012878:Skin Neoplasms / Q000235:genetics*
chemical_list: D005819:Genetic Markers