Increased DNA Methylation at the AXIN1 Gene in a Monozygotic Twin from a Pair Discordant for a Caudal Duplication Anomaly

Oates, Nathan; Vliet, Joke van; Duffy, David L.; Kroes, HY; Martin, Nicholas G.; Boomsma, Dorret I.; Campbell, Megan; Coulthard, Mark G.; Whitelaw, Emma; Chong, Suyinn

doi:10.1086/505031

Cited by 134 publications

(66 citation statements)

References 30 publications

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“…In addition, an individual medical history and immunological experience reflected in differential level of gene hypermethylation could represent an important endogenous factor causing a discordance among genetically identical siblings. 47 Thus, the correlation between our microarray data indicating an involvement of viral infection in the development of diabetes and the appearance of clinically apparent mild respiratory, possibly viral infection in two girls 1 month before clinical diagnosis of T1D is indicative that a viral infection contributed to the autodestructive diabetic process. Although the identity of this viral agent remains uncertain, EV68-71 serotypes positivity points to enteroviruses as obvious suspects.…”

Section: Discussionmentioning

confidence: 51%

Case report: type 1 diabetes in monozygotic quadruplets

et al. 2011

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Type 1 diabetes (T1D) is an autoimmune disease characterized by the lack of insulin due to an autoimmune destruction of pancreatic beta cells. Here, we report a unique case of a family with naturally conceived quadruplets in which T1D was diagnosed in two quadruplets simultaneously. At the same time, the third quadruplet was diagnosed with the pre-diabetic stage. Remarkably, all four quadruplets were positive for anti-islet cell antibodies, GAD65 and IA-A2. Monozygotic status of the quadruplets was confirmed by testing 14 different short tandem repeat polymorphisms. Serological examination confirmed that all quadruplets and their father suffered from a recent enteroviral infection of EV68-71 serotype. To assess the nature of the molecular pathological processes contributing to the development of diabetes, immunocompetent cells isolated from all family members were characterized by gene expression arrays, immune-cell enumerations and cytokine-production assays. The microarray data provided evidence that viral infection, and IL-27 and IL-9 cytokine signalling contributed to the onset of T1D in two of the quadruplets. The propensity of stimulated immunocompetent cells from non-diabetic members of the family to secrete high level of IFN-a further corroborates this conclusion. The number of T regulatory cells as well as plasmacytoid and/or myeloid dendritic cells was found diminished in all family members. Thus, this unique family is a prime example for the support of the so-called 'fertile-field' hypothesis proposing that genetic predisposition to anti-islet autoimmunity is 'fertilized' and precipitated by a viral infection leading to a fully blown T1D.

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Section: Discussionmentioning

confidence: 51%

Case report: type 1 diabetes in monozygotic quadruplets

et al. 2011

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“…Axin1 was found to be methylated in a pair of discordant monozygotic twins with caudal duplication anomaly (OMIM: 607864) (337). Supporting the critical role of Axin2 in craniofacial development, multiple studies in humans have identified polymorphisms/mutations in Axin2 related to tooth agenesis (338)(339)(340)(341) and oral clefts (132,340).…”

Section: Axinmentioning

confidence: 98%

A Comprehensive Overview of Skeletal Phenotypes Associated with Alterations in Wnt/β-catenin Signaling in Humans and Mice

2013

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The Wnt signaling pathway plays key roles in differentiation and development and alterations in this signaling pathway are causally associated with numerous human diseases. While several laboratories were examining roles for Wnt signaling in skeletal development during the 1990s, interest in the pathway rose exponentially when three key papers were published in 2001-2002. One report found that loss of the Wnt co-receptor, Low-density lipoprotein related protein-5 (LRP5), was the underlying genetic cause of the syndrome Osteoporosis pseudoglioma (OPPG). OPPG is characterized by early-onset osteoporosis causing increased susceptibility to debilitating fractures. Shortly thereafter, two groups reported that individuals carrying a specific point mutation in LRP5 (G171V) develop high-bone mass. Subsequent to this, the causative mechanisms for these observations heightened the need to understand the mechanisms by which Wnt signaling controlled bone development and homeostasis and encouraged significant investment from biotechnology and pharmaceutical companies to develop methods to activate Wnt signaling to increase bone mass to treat osteoporosis and other bone disease. In this review, we will briefly summarize the cellular mechanisms underlying Wnt signaling and discuss the observations related to OPPG and the high-bone mass disorders that heightened the appreciation of the role of Wnt signaling in normal bone development and homeostasis. We will then present a comprehensive overview of the core components of the pathway with an emphasis on the phenotypes associated with mice carrying genetically engineered mutations in these genes and clinical observations that further link alterations in the pathway to changes in human bone. Keywords: Wnt signaling; mouse models; Lrp5/Lrp6; β-catenin; skeletal phenotypes Bone Research (2013) 1: 27-71. doi: 10.4248/BR201301004 Overview of Wnt signal transductionWnts are a family of 19 mammalian proteins characterized by a conserved pattern of cysteine residues( 1). Wnts can activate several signaling pathways after binding to their cognate receptors, however, the bulk of this review will focus on the best characterized of these pathways, the so-called canonical pathway (Figure 1). This pathway results in the stabilization of the β-catenin protein and subsequent transactivation of target genes (2). It is initiated by Wnt ligands binding to a receptor complex that includes a member of the Frizzled (Fzd) family of seven-transmembrane receptors and either Lrp5, or the related Lrp6 protein(3). Engagement of this complex results in the phosphorylation of the cytoplasmic domain of Lrp5 or Lrp6, creating a binding site for the Axin protein.In the absence of an upstreamsignal, Axin exists in a multiprotein complex that also includes Adenomatous polyposis coli (APC) and the serine/ threonine protein kinase, Glycogen synthase kinase 3 α/β. This complex facilitates β-catenin for GSK3-dependent phosphorylation, targeting it for ubiquitin-depen- 28 dent proteolysis. Binding of Axin to phosphoryl...

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“…Mill et al (2006) show that even monozygotic twins differ in their epigenetic profiles 1 at age five. Furthermore, their epigenetic differences increase with age and even more so if they have a history of non-shared environments, see Fraga et al (2005) and Oates et al (2006).…”

Section: Empirical Framework: Exploiting Twinsmentioning

confidence: 99%

The family gap in wages: What wombmates reveal

Simonsen¹,

Skipper²

2012

Labour Economics

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Standard-Nutzungsbedingungen:Die Dokumente auf EconStor dürfen zu eigenen wissenschaftlichen Zwecken und zum Privatgebrauch gespeichert und kopiert werden.Sie dürfen die Dokumente nicht für öffentliche oder kommerzielle Zwecke vervielfältigen, öffentlich ausstellen, öffentlich zugänglich machen, vertreiben oder anderweitig nutzen.Sofern die Verfasser die Dokumente unter Open-Content-Lizenzen (insbesondere CC-Lizenzen) zur Verfügung gestellt haben sollten, gelten abweichend von diesen Nutzungsbedingungen die in der dort genannten Lizenz gewährten Nutzungsrechte. www.econstor.eu The Institute for the Study of Labor (IZA) in Bonn is a local and virtual international research center and a place of communication between science, politics and business. IZA is an independent nonprofit organization supported by Deutsche Post Foundation. The center is associated with the University of Bonn and offers a stimulating research environment through its international network, workshops and conferences, data service, project support, research visits and doctoral program. IZA engages in (i) original and internationally competitive research in all fields of labor economics, (ii) development of policy concepts, and (iii) dissemination of research results and concepts to the interested public. Terms of use: Documents in D I S C U S S I O N P A P E R S E R I E SIZA Discussion Papers often represent preliminary work and are circulated to encourage discussion. Citation of such a paper should account for its provisional character. A revised version may be available directly from the author. We shed new light on the effects of having children on hourly wages by exploiting access to data on the entire population of employed same-sex twins in Denmark. Our second contribution is the use of administrative data on absenteeism; the amount of hours off due to holidays and sickness. Our results suggest that childbearing reduces female hourly wages but the principal explanation is in fact mothers' higher levels of absence. We find a positive wage premium for fathers.JEL Classification: J13, J24, J31, J71

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Increased DNA Methylation at the AXIN1 Gene in a Monozygotic Twin from a Pair Discordant for a Caudal Duplication Anomaly

Cited by 134 publications

References 30 publications

Case report: type 1 diabetes in monozygotic quadruplets

Case report: type 1 diabetes in monozygotic quadruplets

A Comprehensive Overview of Skeletal Phenotypes Associated with Alterations in Wnt/β-catenin Signaling in Humans and Mice

The family gap in wages: What wombmates reveal

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