Show simple item record

dc.contributor.authorGodler, DE
dc.contributor.authorTassone, F
dc.contributor.authorLoesch, DZ
dc.contributor.authorTaylor, AK
dc.contributor.authorGehling, F
dc.contributor.authorHagerman, RJ
dc.contributor.authorBurgess, T
dc.contributor.authorGanesamoorthy, D
dc.contributor.authorHennerich, D
dc.contributor.authorGordon, L
dc.contributor.authorEvans, A
dc.contributor.authorChoo, KH
dc.contributor.authorSlater, HR
dc.date.available2014-05-21T22:00:26Z
dc.date.issued2010-04-15
dc.identifierpii: ddq037
dc.identifier.citationGodler, D. E., Tassone, F., Loesch, D. Z., Taylor, A. K., Gehling, F., Hagerman, R. J., Burgess, T., Ganesamoorthy, D., Hennerich, D., Gordon, L., Evans, A., Choo, K. H. & Slater, H. R. (2010). Methylation of novel markers of fragile X alleles is inversely correlated with FMRP expression and FMR1 activation ratio. HUMAN MOLECULAR GENETICS, 19 (8), pp.1618-1632. https://doi.org/10.1093/hmg/ddq037.
dc.identifier.issn0964-6906
dc.identifier.urihttp://hdl.handle.net/11343/28750
dc.descriptionC - Journal Articles
dc.description.abstractThe fragile X syndrome (FXS) is caused by silencing of the fragile X mental retardation gene (FMR1) and the absence of its product, fragile X mental retardation protein (FMRP), resulting from CpG island methylation associated with large CGG repeat expansions (more than 200) termed full mutation (FM). We have identified a number of novel epigenetic markers for FXS using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS), naming the most informative fragile X-related epigenetic element 1 (FREE1) and 2 (FREE2). Methylation of both regions was correlated with that of the FMR1 CpG island detected using Southern blot (FREE1 R = 0.97; P < 0.00001, n = 23 and FREE2 R = 0.93; P < 0.00001, n = 23) and negatively correlated with lymphocyte expression of FMRP (FREE1 R = -0.62; P = 0.01, n = 15 and FREE2 R = -0.55; P = 0.03, n = 15) in blood of partially methylated 'high functioning' FM males. In blood of FM carrier females, methylation of both markers was inversely correlated with the FMR1 activation ratio (FREE1 R = -0.93; P < 0.0001, n = 12 and FREE2 R = -0.95; P < 0.0001, n = 9). In a sample set of 49 controls, 18 grey zone (GZ 40-54 repeats), 22 premutation (PM 55-170 repeats) and 22 (affected) FXS subjects, the FREE1 methylation pattern was consistent between blood and chorionic villi as a marker of methylated FM alleles and could be used to differentiate FXS males and females from controls, as well as from carriers of GZ/PM alleles, but not between GZ and PM alleles and controls. Considering its high-throughput and specificity for pathogenic FM alleles, low cost and minimal DNA requirements, FREE MALDI-TOF MS offers a unique tool in FXS diagnostics and newborn population screening.
dc.languageEnglish
dc.publisherOXFORD UNIV PRESS
dc.subjectNeurology and Neuromuscular Diseases; Expanding Knowledge in the Medical and Health Sciences
dc.titleMethylation of novel markers of fragile X alleles is inversely correlated with FMRP expression and FMR1 activation ratio
dc.typeJournal Article
dc.identifier.doi10.1093/hmg/ddq037
melbourne.affiliationThe University of Melbourne
melbourne.affiliation.departmentMedicine - Royal Melbourne Hospital
melbourne.source.titleHUMAN MOLECULAR GENETICS
melbourne.source.volume19
melbourne.source.issue8
melbourne.source.pages1618-1632
dc.research.codefor110904
dc.research.codeseo2008970111
melbourne.publicationid146342
melbourne.elementsid401963
melbourne.openaccess.pmchttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2846165
melbourne.contributor.authorChoo, Kong
melbourne.contributor.authorSlater, Howard
melbourne.contributor.authorEvans, Andrew
melbourne.contributor.authorGodler, David
melbourne.contributor.authorGANESAMOORTHY, DEVIKA
melbourne.contributor.authorGordon, Lavinia
dc.identifier.eissn1460-2083
melbourne.conference.locationEngland
melbourne.accessrightsAccess this item via the Open Access location


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record