Distribution of human SNPs and its effect on high-throughput genotyping

Hum Mutat. 2006 Mar;27(3):249-54. doi: 10.1002/humu.20286.


Utilizing the results of extensive single nucleotide polymorphism (SNP) studies in humans, stimulated by the International HapMap Project, we present evidence that SNPs are not randomly spaced across the genome, but are somewhat clustered. This observation has important consequences for assay design, since hidden variants in primer sites can affect the accuracy of data. Indeed, using data from the calibration exercises of the HapMap Project, we found instances in which primer site mutations caused allele dropout and other genotyping failures. Given the dynamic nature of SNP discovery, it was inevitable that SNPs would be identified in the primer sites of many assays used for HapMap genotyping. We found that assays with such primer site mutations were correlated with elevated rates of genotype failure and allele dropout. This suggests that taking nearby SNPs into account is important for optimal genotyping assay design.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alleles
  • Base Sequence
  • Binding Sites
  • Calibration
  • Chromosome Mapping / methods*
  • Computational Biology
  • DNA Primers / genetics
  • Genotype*
  • Molecular Sequence Data
  • Mutation
  • Polymorphism, Single Nucleotide*
  • Sequence Analysis, DNA / methods*


  • DNA Primers