Identification and Correction of Sample Mix-Ups in Expression Genetic Data: A Case Study

G3 (Bethesda). 2015 Aug 19;5(10):2177-86. doi: 10.1534/g3.115.019778.

Abstract

In a mouse intercross with more than 500 animals and genome-wide gene expression data on six tissues, we identified a high proportion (18%) of sample mix-ups in the genotype data. Local expression quantitative trait loci (eQTL; genetic loci influencing gene expression) with extremely large effect were used to form a classifier to predict an individual's eQTL genotype based on expression data alone. By considering multiple eQTL and their related transcripts, we identified numerous individuals whose predicted eQTL genotypes (based on their expression data) did not match their observed genotypes, and then went on to identify other individuals whose genotypes did match the predicted eQTL genotypes. The concordance of predictions across six tissues indicated that the problem was due to mix-ups in the genotypes (although we further identified a small number of sample mix-ups in each of the six panels of gene expression microarrays). Consideration of the plate positions of the DNA samples indicated a number of off-by-one and off-by-two errors, likely the result of pipetting errors. Such sample mix-ups can be a problem in any genetic study, but eQTL data allow us to identify, and even correct, such problems. Our methods have been implemented in an R package, R/lineup.

Keywords: eQTL; genetical genomics; microarrays; mislabeling errors; quality control.

Publication types

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

MeSH terms

  • Animals
  • Chromosome Mapping
  • Computational Biology / methods
  • Gene Expression Profiling
  • Gene Expression*
  • Genome-Wide Association Study
  • Genomics / methods
  • Genotype
  • Lod Score
  • Mice
  • Phenotype
  • Quantitative Trait Loci
  • Transcriptome