Four Core Genotypes mice harbour a 3.2MB X-Y translocation that perturbs Tlr7 dosage

Affiliations
  • 1Division of Regulatory Genomics and Cancer Evolution, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • 2Division of Computational Genomics and Systems Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • 3European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
  • 4Division of Artificial Intelligence in Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • 5Department of Integrative Biology & Physiology, University of California, Los Angeles, USA.
  • 6Sex Chromosome Biology Laboratory, The Francis Crick Institute, London, UK.
  • 7European Molecular Biology Laboratory (EMBL), Heidelberg, Germany. edith.heard@embl.org.
  • 8Collège de France, Paris, France. edith.heard@embl.org.
  • 9Division of Regulatory Genomics and Cancer Evolution, German Cancer Research Center (DKFZ), Heidelberg, Germany. d.odom@dkfz.de.

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Abstract

The Four Core Genotypes (FCG) is a mouse model system used to disentangle the function of sex chromosomes and hormones. We report that a copy of a 3.2 MB region of the X chromosome has translocated to the Y chromosome and thus increased the expression of X-linked genes including the single-stranded RNA sensor and autoimmune disease mediator Tlr7. This previously-unreported X-Y translocation complicates the interpretation of studies reliant on C57BL/6J FCG mice.