J Med Genet 47:651-658 doi:10.1136/jmg.2009.069971
  • Original article

Karyomapping: a universal method for genome wide analysis of genetic disease based on mapping crossovers between parental haplotypes

  1. Darren K Griffin4
  1. 1London Bridge Fertility, Gynaecology and Genetics Centre, London, UK
  2. 2Faculty of Biological Sciences, University of Leeds, Leeds, UK
  3. 3Genetics & IVF Institute, Fairfax, Virginia, USA
  4. 4Department of Biosciences, University of Kent, Canterbury, UK
  5. 5Department of Pathology, University of Cambridge, Cambridge, UK
  1. Correspondence to Professor Alan H Handyside, London Bridge Fertility, Gynaecology and Genetics Centre, One St Thomas Street, London SE1 9RY, UK; ahandyside{at}
  • Received 1 June 2009
  • Accepted 29 September 2009
  • Published Online First 25 October 2009


The use of genome wide single nucleotide polymorphism (SNP) arrays for high resolution molecular cytogenetic analysis using a combination of quantitative and genotype analysis is well established. This study demonstrates that by Mendelian analysis of the SNP genotypes of the parents and a sibling or other appropriate family member to establish phase, it is possible to identify informative loci for each of the four parental haplotypes across each chromosome and map the inheritance of these haplotypes and the position of any crossovers in the proband. The resulting ‘karyomap’, unlike a karyotype, identifies the parental and grandparental origin of each chromosome and chromosome segment and is unique for every individual being defined by the independent segregation of parental chromosomes and the pattern of non-recombinant and recombinant chromosomes. Karyomapping, therefore, enables both genome wide linkage based analysis of inheritance and detection of chromosome imbalance where either both haplotypes from one parent are present (trisomy) or neither are present (monosomy/deletion). The study also demonstrates that karyomapping is possible at the single cell level following whole genome amplification and, without any prior patient or disease specific test development, provides a universal linkage based methodology for preimplantation genetic diagnosis readily available worldwide.


  • Funding Self funded.

  • Competing interests A patent application has been submitted by AHH and The Bridge Centre Ltd (PCT/GB2006/004221).

  • Provenance and peer review Not commissioned; externally peer reviewed.