Journal article

Detection of skewed X-chromosome inactivation in Fragile X syndrome and X chromosome aneuploidy using quantitative melt analysis

David E Godler, Yoshimi Inaba, Charles E Schwartz, Quang M Bui, Elva Z Shi, Xin Li, Amy S Herlihy, Cindy Skinner, Randi J Hagerman, David Francis, David J Amor, Sylvia A Metcalfe, John L Hopper, Howard R Slater

EXPERT REVIEWS IN MOLECULAR MEDICINE | CAMBRIDGE UNIV PRESS | Published : 2015

Abstract

Methylation of the fragile X mental retardation 1 (FMR1) exon 1/intron 1 boundary positioned fragile X related epigenetic element 2 (FREE2), reveals skewed X-chromosome inactivation (XCI) in fragile X syndrome full mutation (FM: CGG > 200) females. XCI skewing has been also linked to abnormal X-linked gene expression with the broader clinical impact for sex chromosome aneuploidies (SCAs). In this study, 10 FREE2 CpG sites were targeted using methylation specific quantitative melt analysis (MS-QMA), including 3 sites that could not be analysed with previously used EpiTYPER system. The method was applied for detection of skewed XCI in FM females and in different types of SCA. We tested venous ..

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Grants

Awarded by National Health and Medical Research Council development grant


Awarded by National Institute of Child Health and Human Development grant, USA


Awarded by National Health and Medical Research Council


Awarded by EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT


Funding Acknowledgements

This work was supported by the Victorian Government's Operational Infrastructure Support Program, Murdoch Childrens Research Institute, Royal Children's Hospital Foundation, National Health and Medical Research Council development grant (H.R.S and D.E.G, grant number 1017263), E.W. Al Thrasher Award, USA (to H.R.S and D.E.G), Martin & E.H. Flack Trust, Australia (to H.R.S and D.E.G), Pierce Armstrong Trust (to D.E.G), National Institute of Child Health and Human Development grant, USA (R.J.H, grant number HD36071), National Health and Medical Research Council project grant (H.R.S and D.E.G, grant number 104299), Andrology Australia, Monash University, and in part by a grant from the South Carolina Department of Disabilities and Special Needs (SCDDSN to CES). Dedicated to the memory of Ethan Francis Schwartz 1996-1998.