Journal article
Copy number variation in Y chromosome multicopy genes is linked to a paternal parent-of-origin effect on CNS autoimmune disease in female offspring
Genome biology, v 16(1), pp 28-28
10 Feb 2015
PMID: 25886764
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The prevalence of some autoimmune diseases is greater in females compared with males, although disease severity is often greater in males. The reason for this sexual dimorphism is unknown, but it may reflect negative selection of Y chromosome-bearing sperm during spermatogenesis or male fetuses early in the course of conception/pregnancy. Previously, we showed that the sexual dimorphism in experimental autoimmune encephalomyelitis (EAE) is associated with copy number variation (CNV) in Y chromosome multicopy genes. Here, we test the hypothesis that CNV in Y chromosome multicopy genes influences the paternal parent-of-origin effect on EAE susceptibility in female mice.
We show that C57BL/6 J consomic strains of mice possessing an identical X chromosome and CNV in Y chromosome multicopy genes exhibit sperm head abnormalities and female-biased sex ratio. This is consistent with X-Y intragenomic conflict arising from an imbalance in CNV between homologous X:Y chromosome multicopy genes. These males also display paternal transmission of EAE to female offspring and differential loading of microRNAs within the sperm nucleus. Furthermore, in humans, families of probands with multiple sclerosis similarly exhibit a female-biased sex ratio, whereas families of probands affected with non-sexually dimorphic autoimmune diseases exhibit unbiased sex ratios.
These findings provide evidence for a mechanism at the level of the male gamete that contributes to the sexual dimorphism in EAE and paternal parent-of-origin effects in female mice, raising the possibility that a similar mechanism may contribute to the sexual dimorphism in multiple sclerosis.
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Details
- Title
- Copy number variation in Y chromosome multicopy genes is linked to a paternal parent-of-origin effect on CNS autoimmune disease in female offspring
- Creators
- Laure K Case - Department of Medicine, University of Vermont, Given Medical Building C317, Burlington, VT, 05405, USA. lcase@uvm.eduEmma H Wall - Department of Medicine, University of Vermont, Given Medical Building C317, Burlington, VT, 05405, USA. ewall@uvm.eduErin E Osmanski - Department of Medicine, University of Vermont, Given Medical Building C317, Burlington, VT, 05405, USA. eosmansk@uvm.eduJulie A Dragon - Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT, 05405, USA. jdragon@uvm.eduNaresha Saligrama - Current address: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, 94305, USA. nareshas@stanford.eduJames F Zachary - Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana, IL, 61802, USA. zacharyj@illinois.eduBernardo Lemos - Department of Environmental Health, Harvard School of Public Health, Boston, MA, 02115, USA. blemos@hsph.harvard.eduElizabeth P Blankenhorn - Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, 19129, USA. Libby@DrexelMed.eduCory Teuscher - Department of Pathology, University of Vermont, Burlington, VT, 05405, USA. cteusche@uvm.edu
- Publication Details
- Genome biology, v 16(1), pp 28-28
- Publisher
- Springer BMC; England
- Grant note
- P20 GM103449 / NIGMS NIH HHS R01 NS060901 / NINDS NIH HHS P20RR16462 / NCRR NIH HHS P20 GM103496 / NIGMS NIH HHS NS060901 / NINDS NIH HHS 8P20GM103449 / NIGMS NIH HHS P20 RR016462 / NCRR NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- [Retired Faculty]
- Web of Science ID
- WOS:000369655900001
- Scopus ID
- 2-s2.0-84927148860
- Other Identifier
- 991014878527504721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biotechnology & Applied Microbiology
- Genetics & Heredity