title: No evidence for copy number and methylation variation in H19 and KCNQ10T1 imprinting control regions in children born small for gestational age.
abstract: BACKGROUND
  There is a substantial genetic component for birthweight variation, and although there are known associations between fetal genotype and birthweight, the role of common epigenetic variation in influencing the risk for small for gestational age (SGA) is unknown. The two imprinting control regions (ICRs) located on chromosome 11p15.5, involved in the overgrowth disorder Beckwith-Wiedemann syndrome (BWS) and the growth restriction disorder Silver-Russell syndrome (SRS), are prime epigenetic candidates for regulating fetal growth. We investigated whether common variation in copy number in the BWS/SRS 11p15 region or altered methylation levels at IGF2/H19 ICR or KCNQ10T1 ICR was associated with SGA.
  
  
  METHODS
  We used a methylation-specific multiplex-ligation-dependent probe amplification assay to analyse copy number variation in the 11p15 region and methylation of IGF2/H19 and KCNQ10T1 ICRs in blood samples from 153 children (including 80 SGA), as well as bisulfite pyrosequencing to measure methylation at IGF2 differentially methylated region (DMR)0 and H19 DMR.
  
  
  RESULTS
  No copy number variants were detected in the analyzed cohort. Children born SGA had 2.7% lower methylation at the IGF2 DMR0. No methylation differences were detected at the H19 or KCNQ10T1 DMRs.
  
  
  CONCLUSIONS
  We confirm that a small hypomethylation of the IGF2 DMR0 is detected in peripheral blood leucocytes of children born SGA at term. Copy number variation within the 11p15 BWS/SRS region is not an important cause of non-syndromic SGA at term.
authors.affiliation: Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand. R.Murphy@auckland.ac.nz.
authors.forename: Rinki
authors.initials: R
authors.lastname: Murphy
authors.forename: John Md
authors.initials: JM
authors.lastname: Thompson
authors.forename: Jörg
authors.initials: J
authors.lastname: Tost
authors.forename: Edwin A
authors.initials: EA
authors.lastname: Mitchell
mesh_terms: D001724:Birth Weight / Q000235:genetics*; D016000:Cluster Analysis; D018899:CpG Islands; D056915:DNA Copy Number Variations; D019175:DNA Methylation; D020869:Gene Expression Profiling; D018392:Genomic Imprinting; D006801:Humans; D007236:Infant, Small for Gestational Age; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics*
chemical_list: C094335:H19 long non-coding RNA; C485621:KCNQ1OT1 long non-coding RNA, human; D024642:Potassium Channels, Voltage-Gated; D062085:RNA, Long Noncoding