Cutaneous malignant melanoma and familial dysplastic nevi: Evidence for autosomal dominance and pleiotropy

S. J. Bale, A. Chakravarti, M. H. Greene

Research output: Contribution to journalArticlepeer-review

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 θ = .08. Furthermore, all families giving evidence for linkage were in the coupling phase and the maximum likelihood estimate of θ was not significantly different from O (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.

Original languageEnglish (US)
Pages (from-to)188-196
Number of pages9
JournalAmerican journal of human genetics
Volume38
Issue number2
StatePublished - 1986

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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