Epigenetic and genetic variation at the IGF2/H19 imprinting control region on 11p15.5 is associated with cerebellum weight
Language: 
English
Abstract: 

IGF2 is a paternally expressed imprinted gene with an important role in development and brain function. Allele-specific expression of IGF2 is regulated by DNA methylation at three differentially methylated regions (DMRs) spanning the IGF2/H19 domain on human 11p15.5. We have comprehensively assessed DNA methylation and genotype across the three DMRs and the H19 promoter using tissue from a unique collection of well-characterized and neuropathologically-dissected post-mortem human cerebellum samples (n = 106) and frontal cortex samples (n = 51). We show that DNA methylation, particularly in the vicinity of a key CTCF-binding site (CTCF3) in the imprinting control region (ICR) upstream of H19, is strongly correlated with cerebellum weight. DNA methylation at CTCF3 uniquely explains ~25% of the variance in cerebellum weight. In addition, we report that genetic variation in this ICR is strongly associated with cerebellum weight in a parental-origin specific manner, with maternally-inherited alleles associated with a 16% increase in cerebellum weight compared with paternally-inherited alleles. Given the link between structural brain abnormalities and neuropsychiatric disease, an understanding of the epigenetic and parent-of-origin specific genetic factors associated with brain morphology provides important clues about the etiology of disorders such as schizophrenia and autism.

Author(s): 
Pidsley, Ruth
Dempster, Emma
Troakes, Claire
Al-Sarraj, Safa
Mill, Jonathan
Item Type: 
Journal Article
Publication Title: 
Epigenetics
Journal Abbreviation: 
Epigenetics
Publication Date: 
2012-02
Publication Year: 
2012
Pages: 
155-163
Volume: 
7
Issue: 
2
ISSN: 
1559-2308
DOI: 
10.4161/epi.7.2.18910
Library Catalog: 
PubMed
Extra: 
PMID: 22395465 PMCID: PMC3335909

Turabian/Chicago Citation

Ruth Pidsley, Emma Dempster, Claire Troakes, Safa Al-Sarraj and Jonathan Mill. 2012-02. "Epigenetic and genetic variation at the IGF2/H19 imprinting control region on 11p15.5 is associated with cerebellum weight." Epigenetics 7: 2: 155-163. 10.4161/epi.7.2.18910.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.4161/epi.7.2.18910 | issn = 1559-2308 | volume = 7 | pages = 155-163 | last = Pidsley | first = Ruth | coauthors = Dempster, Emma, Troakes, Claire, Al-Sarraj, Safa, Mill, Jonathan | title = Epigenetic and genetic variation at the IGF2/H19 imprinting control region on 11p15.5 is associated with cerebellum weight | journal = Epigenetics | date = 2012-02 | pmid = | pmc = }} </ref>