Amelogenin-based sex identification as a strategy to control the identity of DNA samples in genetic association studies.
Misassignment between DNA samples and clinical or epidemiological data may compromise the results of genetic association studies. Genotyping in replicates or controlling for Hardy-Weinberg equilibrium cannot identify misassignments caused by sample mix-ups. DNA-based sex identification (sex typing) is currently the best strategy to identify mix-ups. Here we review the available methods and present validated protocols for sex typing. The protocols are based on single-nucleotide differences between the human amelogenin genes, AMELX and AMELY, and are optimized for real-time PCR (TaqMan), primer-extension (SNaPshot) and PCR-RFLP genotyping platforms. In addition, we review the limitations of the sex-typing strategy, including a limited ability to identify single sample mix-ups, the dependence of the power of this approach on the sex distribution in the study population, and rare genetic conditions. Alternative strategies for mix-up identification and possible consequences of mix-up identification are also discussed.
University of Göttingen, Department of Clinical Pharmacology, Robert-Koch-Str. 40, D-37075 Göttingen, Germany. mtzvetk@gwdg.de
Mladen Vassilev
MV
Tzvetkov
Ingolf
I
Meineke
Daniel
D
Sehrt
Stefan Viktor
SV
Vormfelde
Jürgen
J
Brockmöller
D053523:Amelogenin / Q000235:genetics*; D001483:Base Sequence; D004247:DNA / Q000235:genetics* / Q000302:isolation & purification; D017931:DNA Primers / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies / Q000379:methods* / Q000592:standards*; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011786:Quality Control; D012732:Sex Determination Analysis
C507199:AMELX protein, human; C507202:AMELY protein, human; D053523:Amelogenin; D017931:DNA Primers; D004247:DNA