Cheap, accurate and rapid allele frequency estimation of single nucleotide polymorphisms by primer extension and DHPLC in DNA pools

Hum Genet. 2000 Nov;107(5):488-93. doi: 10.1007/s004390000397.


At present, the cost of genotyping single nucleotide polymorphisms (SNPs) in large numbers of subjects poses a formidable problem for molecular genetic approaches to complex diseases. We have tested the possibility of using primer extension and denaturing high performance liquid chromatography to estimate allele frequencies of SNPs in pooled DNA samples. Our data show that this method should allow the accurate estimation of absolute allele frequencies in pooled samples of DNA and also of the difference in allele frequency between different pooled DNA samples. This technique therefore offers an efficient and cheap method for genotyping SNPs in large case-control and family-based association samples.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Base Sequence
  • Chromatography, High Pressure Liquid / economics
  • Chromatography, High Pressure Liquid / methods
  • Chromosomes, Human, Pair 4*
  • Costs and Cost Analysis
  • DNA / chemistry
  • DNA / genetics*
  • DNA Primers
  • Gene Frequency*
  • Genetic Diseases, Inborn / diagnosis
  • Genetic Diseases, Inborn / genetics
  • Homozygote
  • Humans
  • Polymerase Chain Reaction / economics
  • Polymerase Chain Reaction / methods
  • Polymorphism, Genetic*
  • Reproducibility of Results
  • United Kingdom


  • DNA Primers
  • DNA