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Atp10a, a gene adjacent to the PWS/AS gene cluster, is not imprinted in mouse and is insensitive to the PWS-IC

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Abstract

Mutations affecting a cluster of coordinately regulated imprinted genes located at 15q11-q13 underlie both Prader–Willi syndrome (PWS) and Angelman syndrome (AS). Disruption of the predominately maternally expressed UBE3A locus is sufficient to meet diagnostic criteria for AS. However, AS patients with a deletion of the entire PWS/AS locus often have more severe traits than patients with point mutations in UBE3A suggesting that other genes contribute to the syndrome. ATP10A resides 200 kb telomeric to UBE3A and is of uncertain imprinted status. An initial report indicated bialleleic expression of the murine Atp10a in all tissues, but a subsequent report suggests that Atp10a is predominantly maternally expressed in the hippocampus and olfactory bulb. To resolve this discrepancy, we investigated Atp10a allelic expression in the brain, DNA methylation status, and sensitivity to mutations of the PWS imprinting center, an element required for imprinted gene expression in the region. We report that Atp10a is biallelically expressed in both the newborn and adult brain, and Atp10a allelic expression is insensitive to deletion or mutation of the PWS imprinting center. The CpG island associated with Atp10a is hypomethylated, a result consistent with the notion that Atp10a is not an imprinted gene.

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Acknowledgments

We are grateful to Darragh Devine and K. Amy Chen for their help in conducting the brain dissection technique. This work was funded by National Institutes of Health grant HD037872.

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Authors and Affiliations

  1. Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, Florida, 32610-0266, USA

    Amanda J. DuBose, Emily Y. Smith, Ryan A. E. Hallett & James L. Resnick

  2. Institute of Biomedical and Clinical Sciences, Peninsula Medical School, University of Exeter, Exeter, EX2 5DW, UK

    Karen A. Johnstone

Authors
  1. Amanda J. DuBose
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  2. Karen A. Johnstone
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  3. Emily Y. Smith
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  4. Ryan A. E. Hallett
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  5. James L. Resnick
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Correspondence to James L. Resnick.

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DuBose, A.J., Johnstone, K.A., Smith, E.Y. et al. Atp10a, a gene adjacent to the PWS/AS gene cluster, is not imprinted in mouse and is insensitive to the PWS-IC. Neurogenetics 11, 145–151 (2010). https://doi.org/10.1007/s10048-009-0226-9

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