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Apparent human BRCA1 knockout caused by mispriming during polymerase chain reaction: Implications for genetic testing
Author(s) -
Kuschel Bettina,
Gayther Simon A.,
Easton Douglas F.,
Ponder Bruce A. J.,
Pharoah Paul D. P.
Publication year - 2001
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.1122
Subject(s) - polymerase chain reaction , genetics , mutation , polymerase , biology , allele , microbiology and biotechnology , dna , gene
Abstract 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. © 2001 Wiley‐Liss, Inc.