Further evidence for a locus for cutaneous malignant melanoma-dysplastic nevus (CMM/DN) on chromosome 1p, and evidence for genetic heterogeneity

Am J Hum Genet. 1993 Mar;52(3):537-50.


Assignment of a susceptibility locus for cutaneous malignant melanoma-dysplastic nevus (CMM/DN) to chromosome 1p remains controversial. We examined the relationship between CMM/DN and markers D1S47, PND, and D1S160 on seven new families (set B) plus updated versions of six previously reported families (set A). Three linkage analyses were performed: (1) CMM alone--all individuals without confirmed melanoma or borderline lesions were considered unaffected (model I); (2) CMM/DN with variable age at onset and sporadics (model II); and (3) CMM/DN using the model of Bale et al. (model III). For CMM alone and D1S47, Zmax = 3.12 at theta = .10. For D1S160 and CMM alone, Zmax = 1.76 at theta = .10. PND showed no evidence for linkage to CMM alone. Models II and III showed strong evidence for linkage to D1S47, D1S160, and PND in the set A pedigrees but not in the set B families. We tested for homogeneity of CMM/DN (model II) by splitting families into two groups on the basis of (1) the proportion of CMM/DN cases and (2) the occurrence of immune-related tumors. In group 1 there was significant evidence of heterogeneity with both D1S47 and D1S160, and in group 2 there was significant evidence of heterogeneity with D1S160. Thus, diagnostic, clinical, and genetic heterogeneity are the likely reasons that previous studies have failed to confirm linkage of CMM/DN to chromosome 1p. The results showed significant evidence for a CMM locus linked to D1S47, as well as significant evidence for heterogeneity with only a subset of the families appearing linked to chromosome 1p.

MeSH terms

  • Adult
  • Blotting, Southern
  • Chromosomes, Human, Pair 1*
  • DNA / genetics
  • DNA Probes
  • Dysplastic Nevus Syndrome / genetics*
  • Family
  • Female
  • Genetic Linkage
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Pedigree


  • DNA Probes
  • Genetic Markers
  • DNA