Genomic imprinting is an epigenetic marking process that confers parent‐of‐origin‐dependent expression on certain genes. These imprinted genes are sometimes found in clusters, suggesting a possible involvement of higher order regulatory elements controlling expression and imprinting of genes organised in such clusters. In the distal chromosome 7 there are at least four imprinted genes: Mash2, Ins2, Igf2 and H19. Recent evidence(1) suggests that imprinting and expression of at least Igf2 and H19 may be mechanistically linked.

Three recent genome‐wide studies in mice and humans have produced the most definitive map to date of genomic imprinting (gene expression that depends on parental origin) by incorporating multiple tissue types and developmental stages. Here, we explore the results of these studies in light of the kinship theory of genomic imprinting, which predicts that imprinting evolves due to differential genetic relatedness between maternal and paternal relatives. The studies produce a list of imprinted genes with around 120–180 in mice and ∼100 (...) in humans. The studies agree on broad patterns across mice and humans including the complex patterns of imprinted expression at loci like Igf2 and Grb10. We discuss how the kinship theory provides a powerful framework for hypotheses that can explain these patterns. Finally, since imprinting is rare in the genome despite predictions from the kinship theory that it might be common, we discuss evolutionary factors that could favor biallelic expression. (shrink)

Attention is vital to success in all aspects of life (Erickson, Thiessen, Godwin, Dickerson, & Fisher, 2015; Meck & Benson, 2002), hence it is important to identify biomarkers of later attentional problems early enough to intervene. Our objective was to determine if any of 11 genes (APOE, BDNF, HTR4, CHRNA4, COMT, DRD4, IGF2, MAOA, SLC5A7, SLC6A3, and SNAP25) predicted the trajectory of attentional development within the same group of children between infancy and childhood. We recruited followup participants from children (...) who participated as infants in visual attention studies and used a similar task at both time points. Using multilevel modeling, we associated changes in the participant’s position in the distribution of scores in infancy to his/her position in childhood with genetic markers on each of 11 genes. While all 11 genes predicted reaction time (RT) residual scores, only MAOA had a significant interaction including time point. We conclude that the MAOA SNP rs1137070 is useful in predicting which girls are likely to develop slower RTs on an attention task between infancy and childhood. This early identification is likely to be helpful in early intervention. (shrink)

Gene regulation involves various cis-regulatory elements that can act at a distance. They may physically interact each other or with their target genes to exert their effects. Such interactions are beginning to be uncovered in the imprinted Igf2/H19 domain.1 The differentially methylated regions (DMRs), containing insulators, silencers and activators, were shown to have physical contacts between them. The interactions were changeable depending on their epigenetic state, presumably enabling Igf2 to move between an active and a silent chromatin domain. (...) The study gives us a novel view on how regulatory elements influence gene expression and how epigenetic modifications modulate their long-range effects. (shrink)

Human chromosome 11p15 comprises two imprinted domains important in the control of fetal and postnatal growth. Novel studies1-3 establish that imprinting at one of these, the IGF2-H19 domain, is epigenetically deregulated (with loss of DNA methylation) in Silver-Russell Syndrome (SRS), a congenital disease of growth retardation and asymmetry. Previously, the exact opposite epigenetic alteration (gain of DNA methylation) had been detected at the domain's ‘imprinting control region’ (ICR) in patients with Beckwith-Wiedemann Syndrome (BWS), a complex disorder of fetal overgrowth. (...) However, more frequently, BWS is caused by loss of DNA methylation at the ICR that regulates the second imprinted domain at 11p15. Interestingly, a similar epigenetic alteration (with loss of methylation) at a putative ICR on human chromosome 6q24, is involved in transient neonatal diabetes mellitus (TNDM), a congenital disease with intrauterine growth retardation and a transient lack of insulin. Thus, fetal and postnatal growth is epigenetically controlled by different ICRs, at 11p15 and other chromosomal regions. BioEssays 28: 453–459, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

The H19 gene produces a non‐coding RNA, which is abundantly expressed during embryonic development and down‐regulated after birth. Although this gene was discovered over 20 years ago, its function has remained unclear. Only recently a role was identified for the non‐coding RNA and/or its microRNA partner, first as a tumour suppressor gene in mice, then as a trans‐regulator of a group of co‐expressed genes belonging to the imprinted gene network that is likely to control foetal and early postnatal growth in (...) mice. The mechanisms underlying this transcriptional or post‐transcriptional regulation remain to be discovered, perhaps by identifying the protein partners of the full‐length H19 RNA or the targets of the microRNA. This first in vivo evidence of a functional role for the H19 locus provides new insights into how genomic imprinting helps to control embryonic growth. (shrink)