Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
16773576
TITLE
Increased DNA methylation at the AXIN1 gene in a monozygotic twin from a pair discordant for a caudal duplication anomaly.
ABSTRACT
The AXIN1 gene has been implicated in caudal duplication anomalies. Its coding region was sequenced in both members of a monozygotic (MZ) twin pair discordant for a caudal duplication anomaly, but no mutation was found. Using bisulfite sequencing, we examined methylation at the promoter region of the AXIN1 gene in these twins and in twin and age-matched singleton controls. Methylation of the promoter region in peripheral blood mononucleated cells was variable among individuals, including MZ pairs. In the MZ pair discordant for the caudal duplication, this region of the affected twin was significantly more methylated than that of the unaffected twin (P < .0001), which was significantly more methylated than those of the controls (P = .02). We have confirmed that this CpG island does function as a promoter in vitro and that its activity is inversely proportional to the extent of methylation. This finding raises the possibility that hypermethylation of the AXIN1 promoter, by mechanisms as yet undetermined, is associated with the malformation. This case may be paradigmatic for some cases of MZ discordance.
DATE PUBLISHED
2006 Jul
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2005/11/15
accepted 2006/04/05
aheadofprint 2006/05/22
pubmed 2006/06/15 09:00
medline 2006/08/15 09:00
entrez 2006/06/15 09:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Oates NA Oates N A NA School of Molecular and Microbial Biosciences, University of Sydney, Australia.
van Vliet J van Vliet J J
Duffy DL Duffy D L DL
Kroes HY Kroes H Y HY
Martin NG Martin N G NG
Boomsma DI Boomsma D I DI
Campbell M Campbell M M
Coulthard MG Coulthard M G MG
Whitelaw E Whitelaw E E
Chong S Chong S S
INVESTIGATORS
JOURNAL
VOLUME: 79
ISSUE: 1
TITLE: American journal of human genetics
ISOABBREVIATION: Am. J. Hum. Genet.
YEAR: 2006
MONTH: Jul
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Print
ISSN: 0002-9297
ISSNTYPE: Print
MEDLINE JOURNAL
MEDLINETA: Am J Hum Genet
COUNTRY: United States
ISSNLINKING: 0002-9297
NLMUNIQUEID: 0370475
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Axin Protein
Base Sequence
Cauda Equina abnormalities
Cell Line abnormalities
CpG Islands abnormalities
DNA Methylation abnormalities
DNA Primers abnormalities
Humans abnormalities
Promoter Regions, Genetic abnormalities
Repressor Proteins genetics
Twins, Monozygotic genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 AXIN1 protein, human
0 Axin Protein
0 DNA Primers
0 Repressor Proteins
OTHER ID's
OTHERID SOURCE
PMC1474116 NLM