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

Hashemi, Jamileh; Bendahl, Pär-Ola LU ; Törngren, Therese LU ; Platz, Anton; Linder, Stig; Stierner, Ulrika; Olsson, Håkan LU ; Ingvar, Christian LU ; Hansson, Johan and Borg, Åke LU (2001) In Genes, Chromosomes and Cancer 31(2). p.107-116
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Genes, Chromosomes and Cancer
volume
31
issue
2
pages
107 - 116
publisher
John Wiley & Sons
external identifiers
  • pmid:11319798
  • wos:000168470800002
  • scopus:0035020632
ISSN
1045-2257
DOI
10.1002/gcc.1124
language
English
LU publication?
yes
id
d2c6ae02-7d36-494e-a503-0fc06eab961f (old id 1120132)
date added to LUP
2008-06-30 12:36:08
date last changed
2018-05-29 10:29:10
@article{d2c6ae02-7d36-494e-a503-0fc06eab961f,
  abstract     = {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.},
  author       = {Hashemi, Jamileh and Bendahl, Pär-Ola and Törngren, Therese and Platz, Anton and Linder, Stig and Stierner, Ulrika and Olsson, Håkan and Ingvar, Christian and Hansson, Johan and Borg, Åke},
  issn         = {1045-2257},
  language     = {eng},
  number       = {2},
  pages        = {107--116},
  publisher    = {John Wiley & Sons},
  series       = {Genes, Chromosomes and Cancer},
  title        = {Haplotype analysis and age estimation of the 113insR CDKN2A founder mutation in Swedish melanoma families},
  url          = {http://dx.doi.org/10.1002/gcc.1124},
  volume       = {31},
  year         = {2001},
}