Haplotype analysis to determine the position of a mutation among closely linked DNA markers

Michele Ramsay, Robert Williamson, Xavier Estivill, Brandon J. Wainwright, Meng Fatt Ho, Stephanie Halford, Juha Kere, Erkki Savilahti, Albert De La Chapelle, Marianne Schwartz, Martin Schwartz, Maurice Super, Peter Farndon, Carol Harding, Linda Meredith, Layla Al-Jader, Claude Ferec, Mireille Claustres, Teresa Casals, Virginia NunesPaolo Gasparini, Anna Savoia, Pier Franco Pignatti, Gluseppe Novelli, Massimo Bennarelli, Bruno Dallapiccola, Luba Kalaydjieva, Peter J. Scambler

Research output: Contribution to journalArticlepeer-review


Positional cloning involves first finding linkage between an inherited phenotype (such as a disease) and a DNA marker, followed by the use of a variety of physical and genetic mapping techniques to move from linkage to mutation. If there is a founder effect within a population, crossovers are often rare between the mutation causing the phenotype and closely situated markers and increasing disequilibrium may be observed as the site of the mutation is approached. Standard coefficients of disequilibrium may, however, be insensitive to the relative position of close markers and the mutation, because they depend upon allele frequencies in the normal population compared to those of the founder chromosome. Using cystic fibrosis in European populations as a model system, alternative methods for determining the position of a mutation are discussed. These include haplotype parsimony and three-way interval likelihood analysis. Both methods predict the location of the major CF mutation accurately from a real set of more than 600 European CF chromosomes.

Original languageEnglish
Pages (from-to)1007-1014
Number of pages8
JournalHuman Molecular Genetics
Issue number7
Publication statusPublished - Jul 1993

ASJC Scopus subject areas

  • Genetics
  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Public Health, Environmental and Occupational Health
  • Molecular Biology
  • Genetics(clinical)


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