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Cited by 63Genomic variations and chromosomal abnormalitiesGenetic diversity and population structureGenomics and Phylogenetic Studies

SNP array profiling of mouse cell lines identifies their strains of origin and reveals cross-contamination and widespread aneuploidy

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Didion, John P, Buus, Ryan J, Naghashfar, Zohreh, Threadgill, David W, Morse, Herbert C, de Villena, Fernando Pardo-Manuel·2014·BMC Genomics
DOI 10.1186/1471-2164-15-847PMC PMC4198738
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Abstract

BACKGROUND: The crisis of Misidentified and contaminated cell lines have plagued the biological research community for decades. Some repositories and journals have heeded calls for mandatory authentication of human cell lines, yet misidentification of mouse cell lines has received little publicity despite their importance in sponsored research. Short tandem repeat (STR) profiling is the standard authentication method, but it may fail to distinguish cell lines derived from the same inbred strain of mice. Additionally, STR profiling does not reveal karyotypic changes that occur in some high-passage lines and may have functional consequences. Single nucleotide polymorphism (SNP) profiling has been suggested as a more accurate and versatile alternative to STR profiling; however, a high-throughput method for SNP-based authentication of mouse cell lines has not been described. RESULTS: We have developed computational methods (Cell Line Authentication by SNP Profiling, CLASP) for cell line authentication and copy number analysis based on a cost-efficient SNP array, and we provide a reference database of commonly used mouse strains and cell lines. We show that CLASP readily discriminates among cell lines of diverse taxonomic origins, including multiple cell lines derived from a single inbred strain, intercross or wild caught mouse. CLASP is also capable of detecting contaminants present at concentrations as low as 5%. Of the 99 cell lines we tested, 15 exhibited substantial divergence from the reported genetic background. In all cases, we were able to distinguish whether the authentication failure was due to misidentification (one cell line, Ba/F3), the presence of multiple strain backgrounds (five cell lines), contamination by other cells and/or the presence of aneuploid chromosomes (nine cell lines). CONCLUSIONS: Misidentification and contamination of mouse cell lines is potentially as widespread as it is in human cell culture. This may have substantial implications for studies that are dependent on the expected background of their cell cultures. Laboratories can mitigate these risks by regular authentication of their cell cultures. Our results demonstrate that SNP array profiling is an effective method to combat cell line misidentification.

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  • For mouse, MUGA can be combined with CLASP for cell line authentication and copy number analysis.

    “For mouse there is a Mouse Universal Genotyping Array (MUGA) available that can be combined with a computational method called Cell Line Authentication by SNP Profiling (CLASP) for cell line authentication and copy number analysis [66].”

    From Genetic Insights into the Economic Toll of Cell Line Misidentification: A Comprehensive Review (2026) · cites this paper as [66]

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Authors
Didion, J. P., Buus, R. J., Naghashfar, Z., Threadgill, D. W., Morse, H. C., & de Villena, F. P.-M.
Affiliations
  • University of North Carolina at Chapel Hill (US)
  • National Institutes of Health (US)
  • Texas A&M University (US)
Corresponding author
Morse, Herbert C
ORCID
Venue
BMC Genomics
Publisher
Springer Science and Business Media LLC
Published
2014-10-03
Volume
15
Issue
1
Pages
847-847
ISSN
1471-2164 (ISSN-L)
DOI
10.1186/1471-2164-15-847
PMC
PMC4198738
OpenAlex
W2010153950
Cited by
63
References
3
Citations by year
2026: 2 · 2025: 3 · 2024: 5 · 2023: 3 · 2022: 4 · 2021: 3 · 2020: 4 · 2019: 5 · 2018: 17 · 2017: 7 · 2016: 5 · 2015: 5
FWCI
3.72
Type
journal article
Language
en
Open access
Licence
Locations
  • BMC Genomics (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion, cc-by)
  • Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
  • OakTrust (Texas A&M University Libraries) (submittedVersion)
  • UNC Libraries
Funders
  • National Institutes of Health
  • National Institute of Mental Health (P50MH090338)
  • National Human Genome Research Institute (P50HG006582)
  • National Institute of General Medical Sciences (T32GM067553, GM067553-04)
  • National Institute of Allergy and Infectious Diseases
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic diversity and population structure
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
Keywords
mouse cell lines, cell line authentication, cell line misidentification, cross-contamination, aneuploidy, SNP array, copy number analysis, CLASP, inbred mouse strains, karyotype
MeSH terms
Aneuploidy, Animals, Cell Line, Crosses, Genetic, Genotype, Mice, Inbred Strains, Linkage Disequilibrium, Microsatellite Repeats, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, Gene Expression Profiling, Mice, DNA Copy Number Variations

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