Human Molecular Genetics Advance Access published online on November 25, 2003
Human Molecular Genetics, doi:10.1093/hmg/ddh013
© 2003 by Oxford University Press
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Laboratory of Developmental Genetics and Imprinting, Developmental Genetics Programme, The Babraham Institute, Cambridge, CB2 4AT
* To whom correspondence should be addressed. E-mail: wolf.reik{at}bbsrc.ac.uk.
Beckwith Wiedemann syndrome (BWS) is a fetal overgrowth disorder involving the deregulation of a number of genes, including IGF2 and CDKN1C, in the imprinted gene cluster on chromosome 11p15.5. In sporadic BWS cases the majority of patients have epimutations in this region. Loss of imprinting of the IGF2 gene is frequently observed in BWS, as is reduced CDKN1C expression related to loss of maternal allele-specific methylation (LOM) of the differentially methylated region KvDMR1. The causes of epimutations are unknown, although recently an association with assisted reproductive technologies has been described. To date the only genetic mutations described in BWS are in the CDKN1C gene. In order to screen for other genetic predispositions to BWS, the conserved sequences between human and mouse differentially methylated regions (DMRs) of the IGF2 gene were analysed for variants. Four single nucleotide polymorphisms (SNPs) were found in DMR0 (T123C, G358A, T382G, and A402G) which occurred in three out of 16 possible haplotypes: TGTA, CATG and CAGA. DNA samples from a cohort of sporadic BWS patients and healthy controls were genotyped for the DMR0 SNPs. There was a significant increase in the frequency of the CAGA haplotype and a significant decrease in the frequency of the CATG haplotype in the patient cohort compared to controls. These associations were still significant in a BWS subgroup with KvDMR1 LOM, suggesting that the G allele at T382G SNP (CAGA haplotype) is associated with LOM at KvDMR1. This indicates either a genetic predisposition to LOM, or interactions between genotype and epigenotype that impinge on the disease phenotype.
Article
An association between variants in the IGF2 gene and Beckwith-Wiedemann Syndrome: Interaction between genotype and epigenotype
2 Section of Medical and Molecular Genetics, Department of Paediatrics and Child Health, The Medical School, The University of Birmingham, Birmingham B15 2TT
3 Laboratory of Developmental Genetics and Imprinting, Developmental Genetics Programme, The Babraham Institute, Cambridge, CB2 4AT; The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA
4 Institute of Reproductive and Developmental Biology, Faculty of Medicine, Imperial College London, Hammersmith Campus, Du Cane Road, London. W12 0NN
5 Institute of Reproductive and Developmental Biology, Faculty of Medicine, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN
6 Section of Medical and Molecular Genetics, Department of Paediatrics and Child Health, The Medical School, The University of Birmingham, Birmingham, B15 2TT
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  E. Schilling, C. El Chartouni, and M. Rehli Allele-specific DNA methylation in mouse strains is mainly determined by cis-acting sequences Genome Res., November 1, 2009; 19(11): 2028 - 2035. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Murphy, J. Baptista, J. Holly, A. M. Umpleby, S. Ellard, L. W. Harries, J. Crolla, T. Cundy, and A. T. Hattersley Severe Intrauterine Growth Retardation and Atypical Diabetes Associated with a Translocation Breakpoint Disrupting Regulation of the Insulin-Like Growth Factor 2 Gene J. Clin. Endocrinol. Metab., November 1, 2008; 93(11): 4373 - 4380. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Ogino, A. Hazra, G. J. Tranah, G. J. Kirkner, T. Kawasaki, K. Nosho, M. Ohnishi, Y. Suemoto, J. A. Meyerhardt, D. J. Hunter, et al. MGMT germline polymorphism is associated with somatic MGMT promoter methylation and gene silencing in colorectal cancer Carcinogenesis, September 1, 2007; 28(9): 1985 - 1990. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Heude, K. K. Ong, R. Luben, N. J. Wareham, and M. S. Sandhu Study of Association between Common Variation in the Insulin-Like Growth Factor 2 Gene and Indices of Obesity and Body Size in Middle-Aged Men and Women J. Clin. Endocrinol. Metab., July 1, 2007; 92(7): 2734 - 2738. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Fradin, S. Heath, J. Lepercq, M. Lathrop, and P. Bougneres Identification of Distinct Quantitative Trait Loci Affecting Length or Weight Variability at Birth in Humans J. Clin. Endocrinol. Metab., October 1, 2006; 91(10): 4164 - 4170. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. E. Murphy, R. Smith, W. B. Giles, and V. L. Clifton Endocrine Regulation of Human Fetal Growth: The Role of the Mother, Placenta, and Fetus Endocr. Rev., April 1, 2006; 27(2): 141 - 169. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Horsthemke and M. Ludwig Assisted reproduction: the epigenetic perspective Hum. Reprod. Update, September 1, 2005; 11(5): 473 - 482. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Murrell, V. K. Rakyan, and S. Beck From genome to epigenome Hum. Mol. Genet., April 15, 2005; 14(suppl_1): R3 - R10. [Abstract] [Full Text] [PDF]
|
|