Apparent human BRCA1 knockout caused by mispriming during polymerase chain reaction: implications for genetic testing

Genes Chromosomes Cancer. 2001 May;31(1):96-8. doi: 10.1002/gcc.1122.


We report an apparent BRCA1 homozygous knockout that, on further analysis, was found to be an artefact of the polymerase chain reaction. This finding has two important implications. First, it challenges results of a previous study that reported a homozygous knockout associated with the same BRCA1 mutation. Second, our findings suggest that mispriming caused by mismatched primers at the site of single-nucleotide polymorphisms, leading to preferential amplification of one allele, may represent a significant proportion of instances of mutation-detection insensitivity. This may have major implications for the sensitivity of all polymerase chain reaction-based mutation-detection methods in clinical genetic testing laboratories.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Artifacts
  • Chromosome Deletion*
  • DNA Primers*
  • Genes, BRCA1 / genetics*
  • Genetic Carrier Screening / methods
  • Genetic Testing / standards
  • Heteroduplex Analysis / standards
  • Humans
  • Polymerase Chain Reaction* / standards


  • DNA Primers