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Updated: Aug 8, 2026

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
Published on: August 20, 2019
The callipyge mutation enhances bidirectional long-range DLK1-GTL2 intergenic transcription in cis
Haruko Takeda1, Florian Caiment, Maria Smit
1Unit of Animal Genetics, Faculty of Veterinary Medicine and Centre of Biomedical Integrative Genoproteomics (CBIG), University of Liège (B43), 20 Boulevard de Colonster, 4000-Liège, Belgium.
Abstract:
The callipyge mutation (CLPG) is an A to G transition that affects a muscle-specific long-range control element located in the middle of the 90-kb DLK1-GTL2 intergenic (IG) region. It causes ectopic expression of a 327-kb cluster of imprinted genes in skeletal muscle, resulting in the callipyge muscular hypertrophy and its non-Mendelian inheritance pattern known as polar overdominance. We herein demonstrate that the CLPG mutation alters the muscular epigenotype of the DLK1-GTL2 IG region in cis, including hypomethylation, acquisition of novel DNase-I hypersentivite sites, and, most strikingly, strongly enhanced bidirectional, long-range IG transcription. The callipyge phenotype thus emerges as a unique model to study the functional significance of IG transcription, which recently has proven to be a widespread, yet elusive, feature of the mammalian genome.
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