Article Text

ANALYSIS OF THE IMPRINTED GENE ZAC1 AND THE 6Q24-Q25 REGION IN FETAL GROWTH
  1. I IglesiasPlatas1,
  2. D Monk2,3,
  3. M Iriondo1,
  4. A MartinAncel1,
  5. J M Lailla4,
  6. G E Moore3
  1. 1Neonatal Unit, Hospital Sant Joan de Deu, Barcelona, Spain
  2. 2Cancer Epigenetics and Biology Program, Institut Catala D’Oncologia, Barcelona, Spain
  3. 3Clinical and Molecular Genetics Unit, Institute of Child Health, London, UK
  4. 4Gynaecology and Obstetrics Service, Hospital Sant Joan de Deu, Barcelona, Spain

Abstract

Fetal growth is a complex, dynamic process controlled by a wide range of maternal, placental and fetal influences. As a result, the aetiology of intrauterine growth restriction (IUGR) is often multifactorial, involving both genetic and environmental factors. In early fetal life, the major determinant of growth is the fetal genome, but later in pregnancy, environment, nutrition and hormonal factors become increasingly important.

In this study, we have assessed the involvement of genomic imprinting, specifically of genes mapping to the human chromosome 6-imprinted domain. Genomic imprinting is an epigenetic mechanism of regulation that results in parent-of-origin expression. It is an important regulatory pathway involved in the development and function of the placenta. Presently, genomic imprinting is understood to be a mechanism aimed at controlling the amount of maternal resources allocated to the offspring from conception to weaning.

The human chromosome 6-imprinted domain contains the paternally expressed ZAC1/PLAGL1 gene. Loss-of-imprinting of ZAC1/PLAGL1 in humans leads to IUGR and transient neonatal diabetes mellitus. Intriguingly loss of expression in mouse models also results in IUGR, suggesting that aberrant fluctuation of ZAC expression influences a network that regulates fetal growth. To characterize the extent of this imprinted domain, we have assessed the parent-of-origin expression for 10 additional genes mapping to this interval. In addition, to gain insights into the physiological relevance of ZAC1/PLAGL1 in normal growth, we have assessed the expression levels of the various ZAC isoforms and the DNA methylation profile of the ZAC1/HYMAI promoter in a cohort of 120 consecutively collected placenta samples.

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