Gender influences monoallelic expression of ATP10A in human brain
- 23 August 2008
- journal article
- research article
- Published by Springer Science and Business Media LLC in Human Genetics
- Vol. 124 (3), 235-242
- https://doi.org/10.1007/s00439-008-0546-0
Abstract
Human chromosome 15q11–13 and the syntenic region of mouse chromosome 7 contain multiple imprinted genes necessary for proper neurodevelopment. Due to imprinting, paternal 15q11–13 deficiencies lead to Prader-Willi syndrome (PWS) while maternal 15q11–13 deficiencies cause Angelman syndrome (AS). The mechanisms involved in parental imprinting of this locus are conserved between human and mouse, yet inconsistencies exist in reports of imprinting of the maternally expressed gene Atp10a/ATP10A. Excess maternal 15q11–13 dosage often leads to autism-spectrum disorder therefore further investigation to characterize the true imprinting status of ATP10A in humans was warranted. In this study, we examined allelic expression of ATP10A transcript in 16 control brain samples, and found that 10/16 exhibited biallelic expression while only 6/16 showed monoallelic expression. Contrary to the expectation for a maternally expressed imprinted gene, quantitative RT-PCR revealed significantly reduced ATP10A transcript in Prader-Willi syndrome brains with two maternal chromosomes due to uniparental disomy (PWS UPD). Furthermore, a PWS UPD brain sample with monoallelic ATP10A expression demonstrated that monoallelic expression can be independent of imprinting. Investigation of factors that may influence allelic ATP10A expression status revealed that gender has a major affect, as females were significantly more likely to have monoallelic ATP10A expression than males. Regulatory sequences were also examined, and a promoter polymorphism that disrupts binding of the transcription factor Sp1 also potentially contributes to allelic expression differences in females. Our results show that monoallelic expression of human ATP10A is variable in the population and is influenced by both gender and common genetic variation.Keywords
This publication has 31 references indexed in Scilit:
- Neurons but not glial cells show reciprocal imprinting of sense and antisense transcripts of Ube3aHuman Molecular Genetics, 2003
- Predominant maternal expression of the mouse Atp10c in hippocampus and olfactory bulbJournal of Human Genetics, 2003
- Characterization of a putative type IV aminophospholipid transporter P-type ATPaseMammalian Genome, 2003
- Distinct phenotypes distinguish the molecular classes of Angelman syndromeJournal of Medical Genetics, 2001
- Genome Organization, Function, and Imprinting in Prader-Willi and Angelman SyndromesAnnual Review of Genomics and Human Genetics, 2001
- The Human Aminophospholipid-Transporting ATPase Gene ATP10C Maps Adjacent to UBE3A and Exhibits Similar Imprinted ExpressionAmerican Journal of Human Genetics, 2001
- Molecular characterisation of four cases of intrachromosomal triplication of chromosome 15q11-q14Journal of Medical Genetics, 2001
- A novel ATPase on mouse chromosome 7 is a candidate gene for increased body fatPhysiological Genomics, 2000
- Origin of uniparental disomy 15 in patients with Prader-Willi or Angelman syndromeAmerican Journal of Medical Genetics, 2000
- Prader-Willi and Angelman syndromes: Sister imprinted disordersAmerican Journal of Medical Genetics, 2000