PT  - JOURNAL ARTICLE
AU  - Alan H Handyside
AU  - Gary L Harton
AU  - Brian Mariani
AU  - Alan R Thornhill
AU  - Nabeel Affara
AU  - Marie-Anne Shaw
AU  - Darren K Griffin
TI  - Karyomapping: a universal method for genome wide analysis of genetic disease based on mapping crossovers between parental haplotypes
AID  - 10.1136/jmg.2009.069971
DP  - 2010 Oct 01
TA  - Journal of Medical Genetics
PG  - 651--658
VI  - 47
IP  - 10
4099  - http://jmg.bmj.com/content/47/10/651.short
4100  - http://jmg.bmj.com/content/47/10/651.full
SO  - J Med Genet2010 Oct 01; 47
AB  - 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.