Haplotype analysis and age estimation of the 113insR CDKN2A founder mutation in Swedish melanoma families

Genes Chromosomes Cancer. 2001 Jun;31(2):107-16. doi: 10.1002/gcc.1124.


Germline mutations in the CDKN2A tumor suppressor gene located on 9p21 have been linked to development of melanomas in some families. A germline 3-bp insertion in exon 2 of CDKN2A, leading to an extra arginine at codon 113 (113insR), has been identified in 17 Swedish melanoma families. Analysis of 10 microsatellite markers, spanning approximately 1 Mbp in the 9p21 region, showed that all families share a common allele for at least one of the markers closest to the CDKN2A gene, suggesting that the 113insR mutation is an ancestral founder mutation. Differences in the segregating haplotypes, due to meiotic recombinations and/or mutations in the short-tandem-repeat markers, were analyzed further to estimate the age of the mutation. Statistical analysis using a maximum likelihood approach indicated that the mutation arose 98 generations (90% confidence interval: 52-167 generations), or approximately 2,000 years, ago. Thus, 113insR would be expected to have a more widespread geographic distribution in European and North American regions with ancestral connections to Sweden. Alternatively, CDKN2A may lie in a recombination hot spot region, as suggested by the many meiotic recombinations in this narrow approximately 1-cM region on 9p21.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Arginine / genetics*
  • Female
  • Founder Effect*
  • Gene Frequency
  • Genes, p16 / genetics*
  • Genetic Carrier Screening
  • Haplotypes*
  • Humans
  • Likelihood Functions
  • Male
  • Melanoma / genetics*
  • Mutagenesis, Insertional / genetics*
  • Mutation / genetics*
  • Sweden


  • Arginine