Use of single nucleotide polymorphisms (SNP) and real-time polymerase chain reaction for bone marrow engraftment analysis

J Mol Diagn. 2000 Nov;2(4):202-8. doi: 10.1016/S1525-1578(10)60638-1.

Abstract

Allogeneic bone marrow transplant engraftment assays use polymorphisms in the human genome to determine the relative percentages of donor and recipient cells present in the recipient. We describe a novel posttransplant assay approach using single nucleotide polymorphisms (SNPs), the most common type of polymorphism in humans. Using samples of defined genotype, we used real-time polymerase chain reaction (PCR) and allele-specific fluorescent TaqMan probes to assay a SNP of the cytochrome P450 CYP2C9 gene. Standard curves of chimeric mixes showed a linear relationship between the ratio of two alleles and the ratio of their respective fluorophore emission, except for mixes with a low percentage (< 5%) of the less common allele. We validated the SNP real-time PCR assay by comparing it to Southern hybridization analysis, analyzing DNA mixes in a blinded fashion with both methods. The correlation between the two methods was high. We have produced a statistical model that varies allele frequency to predict how many SNPs would be required to produce a functional SNP panel. Additional development will be necessary to produce such a panel of highly informative SNPs for clinical use. A real-time PCR SNP assay may ultimately provide more accurate quantification and shortened turnaround time compared to current post-engraftment assays.

Publication types

  • Evaluation Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Aryl Hydrocarbon Hydroxylases*
  • Blotting, Southern
  • Bone Marrow Transplantation*
  • Cytochrome P-450 CYP2C9
  • Cytochrome P-450 Enzyme System / genetics
  • DNA / blood
  • Graft Survival*
  • Humans
  • Molecular Probes
  • Polymerase Chain Reaction / methods*
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single Nucleotide*
  • Reproducibility of Results
  • Steroid 16-alpha-Hydroxylase*
  • Steroid Hydroxylases / genetics

Substances

  • Molecular Probes
  • DNA
  • Cytochrome P-450 Enzyme System
  • Steroid Hydroxylases
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • Aryl Hydrocarbon Hydroxylases
  • Steroid 16-alpha-Hydroxylase