title: Chimerism analysis in transplant patients: a hypothesis-free approach in the absence of reference genotypes.
abstract: BACKGROUND
  During routine analysis of chimerism in bone marrow transplant patients pre-transplant genotype of the recipient or the donor might lack. We aimed to develop a new method to analyze DNA results suitable when reference genotypes are not available.
  
  
  METHODS
  The method was based on the balance between heterozygotes. It was implemented in a standard computer spreadsheet, and considered the hypothetical donor-recipient genotype combinations. Hypotheses with peak height ratios and allele sharing tendency above a critical threshold were accepted. The results were compared with those obtained with prior knowledge of reference genotypes.
  
  
  RESULTS
  The algorithm predicted correctly the proportion of donor/recipient chimerism, even in the absence of reference genotypes. In fact, the predicted values were closely correlated (r(2)>0.98) and free of systematic bias (slope 0.98-1.04), in comparison with the reference values obtained with prior knowledge of the donor and recipient genetic profiles.
  
  
  CONCLUSIONS
  This study constitutes a proof-of-concept of the application of the heterozygote balance for the quantitative study of chimerism. The algorithm computes post-transplant chimerism in an easy and time-efficient way, even when the donor and recipient reference genotypes are unavailable. Therefore, it can be a useful tool for laboratories involved in chimerism analysis.
authors.affiliation: Unit of Legal Medicine, University of Cantabria, Av Herrera Oria s/n, 39011 Santander, Spain.
authors.forename: Adrian
authors.initials: A
authors.lastname: Odriozola
authors.forename: José A
authors.initials: JA
authors.lastname: Riancho
authors.forename: Raul
authors.initials: R
authors.lastname: Nozal
authors.forename: Arancha
authors.initials: A
authors.lastname: Bermúdez
authors.forename: Ana
authors.initials: A
authors.lastname: Santurtún
authors.forename: Jana
authors.initials: J
authors.lastname: Arozamena
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Zarrabeitia
mesh_terms: D000465:Algorithms; D000483:Alleles; D001322:Autoanalysis; D016026:Bone Marrow Transplantation; D019295:Computational Biology; D004247:DNA / Q000235:genetics*; D005838:Genotype; D006801:Humans; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D018183:Transplantation Chimera / Q000235:genetics*
chemical_list: D004247:DNA