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The role and interaction of imprinted genes in human fetal growth
Identifying the genetic input for fetal growth will help to understand common, serious complications of pregnancy such as fetal growth restriction. Genomic imprinting is an epigenetic process that silences one parental allele, resulting in monoallelic expression. Imprinted genes are important in mam...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4305174/ https://www.ncbi.nlm.nih.gov/pubmed/25602077 http://dx.doi.org/10.1098/rstb.2014.0074 |
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author | Moore, Gudrun E. Ishida, Miho Demetriou, Charalambos Al-Olabi, Lara Leon, Lydia J. Thomas, Anna C. Abu-Amero, Sayeda Frost, Jennifer M. Stafford, Jaime L. Chaoqun, Yao Duncan, Andrew J. Baigel, Rachel Brimioulle, Marina Iglesias-Platas, Isabel Apostolidou, Sophia Aggarwal, Reena Whittaker, John C. Syngelaki, Argyro Nicolaides, Kypros H. Regan, Lesley Monk, David Stanier, Philip |
author_facet | Moore, Gudrun E. Ishida, Miho Demetriou, Charalambos Al-Olabi, Lara Leon, Lydia J. Thomas, Anna C. Abu-Amero, Sayeda Frost, Jennifer M. Stafford, Jaime L. Chaoqun, Yao Duncan, Andrew J. Baigel, Rachel Brimioulle, Marina Iglesias-Platas, Isabel Apostolidou, Sophia Aggarwal, Reena Whittaker, John C. Syngelaki, Argyro Nicolaides, Kypros H. Regan, Lesley Monk, David Stanier, Philip |
author_sort | Moore, Gudrun E. |
collection | PubMed |
description | Identifying the genetic input for fetal growth will help to understand common, serious complications of pregnancy such as fetal growth restriction. Genomic imprinting is an epigenetic process that silences one parental allele, resulting in monoallelic expression. Imprinted genes are important in mammalian fetal growth and development. Evidence has emerged showing that genes that are paternally expressed promote fetal growth, whereas maternally expressed genes suppress growth. We have assessed whether the expression levels of key imprinted genes correlate with fetal growth parameters during pregnancy, either early in gestation, using chorionic villus samples (CVS), or in term placenta. We have found that the expression of paternally expressing insulin-like growth factor 2 (IGF2), its receptor IGF2R, and the IGF2/IGF1R ratio in CVS tissues significantly correlate with crown–rump length and birthweight, whereas term placenta expression shows no correlation. For the maternally expressing pleckstrin homology-like domain family A, member 2 (PHLDA2), there is no correlation early in pregnancy in CVS but a highly significant negative relationship in term placenta. Analysis of the control of imprinted expression of PHLDA2 gave rise to a maternally and compounded grand-maternally controlled genetic effect with a birthweight increase of 93/155 g, respectively, when one copy of the PHLDA2 promoter variant is inherited. Expression of the growth factor receptor-bound protein 10 (GRB10) in term placenta is significantly negatively correlated with head circumference. Analysis of the paternally expressing delta-like 1 homologue (DLK1) shows that the paternal transmission of type 1 diabetes protective G allele of rs941576 single nucleotide polymorphism (SNP) results in significantly reduced birth weight (−132 g). In conclusion, we have found that the expression of key imprinted genes show a strong correlation with fetal growth and that for both genetic and genomics data analyses, it is important not to overlook parent-of-origin effects. |
format | Online Article Text |
id | pubmed-4305174 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | The Royal Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-43051742015-03-05 The role and interaction of imprinted genes in human fetal growth Moore, Gudrun E. Ishida, Miho Demetriou, Charalambos Al-Olabi, Lara Leon, Lydia J. Thomas, Anna C. Abu-Amero, Sayeda Frost, Jennifer M. Stafford, Jaime L. Chaoqun, Yao Duncan, Andrew J. Baigel, Rachel Brimioulle, Marina Iglesias-Platas, Isabel Apostolidou, Sophia Aggarwal, Reena Whittaker, John C. Syngelaki, Argyro Nicolaides, Kypros H. Regan, Lesley Monk, David Stanier, Philip Philos Trans R Soc Lond B Biol Sci Articles Identifying the genetic input for fetal growth will help to understand common, serious complications of pregnancy such as fetal growth restriction. Genomic imprinting is an epigenetic process that silences one parental allele, resulting in monoallelic expression. Imprinted genes are important in mammalian fetal growth and development. Evidence has emerged showing that genes that are paternally expressed promote fetal growth, whereas maternally expressed genes suppress growth. We have assessed whether the expression levels of key imprinted genes correlate with fetal growth parameters during pregnancy, either early in gestation, using chorionic villus samples (CVS), or in term placenta. We have found that the expression of paternally expressing insulin-like growth factor 2 (IGF2), its receptor IGF2R, and the IGF2/IGF1R ratio in CVS tissues significantly correlate with crown–rump length and birthweight, whereas term placenta expression shows no correlation. For the maternally expressing pleckstrin homology-like domain family A, member 2 (PHLDA2), there is no correlation early in pregnancy in CVS but a highly significant negative relationship in term placenta. Analysis of the control of imprinted expression of PHLDA2 gave rise to a maternally and compounded grand-maternally controlled genetic effect with a birthweight increase of 93/155 g, respectively, when one copy of the PHLDA2 promoter variant is inherited. Expression of the growth factor receptor-bound protein 10 (GRB10) in term placenta is significantly negatively correlated with head circumference. Analysis of the paternally expressing delta-like 1 homologue (DLK1) shows that the paternal transmission of type 1 diabetes protective G allele of rs941576 single nucleotide polymorphism (SNP) results in significantly reduced birth weight (−132 g). In conclusion, we have found that the expression of key imprinted genes show a strong correlation with fetal growth and that for both genetic and genomics data analyses, it is important not to overlook parent-of-origin effects. The Royal Society 2015-03-05 /pmc/articles/PMC4305174/ /pubmed/25602077 http://dx.doi.org/10.1098/rstb.2014.0074 Text en http://creativecommons.org/licenses/by/4.0/ © 2015 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited. |
spellingShingle | Articles Moore, Gudrun E. Ishida, Miho Demetriou, Charalambos Al-Olabi, Lara Leon, Lydia J. Thomas, Anna C. Abu-Amero, Sayeda Frost, Jennifer M. Stafford, Jaime L. Chaoqun, Yao Duncan, Andrew J. Baigel, Rachel Brimioulle, Marina Iglesias-Platas, Isabel Apostolidou, Sophia Aggarwal, Reena Whittaker, John C. Syngelaki, Argyro Nicolaides, Kypros H. Regan, Lesley Monk, David Stanier, Philip The role and interaction of imprinted genes in human fetal growth |
title | The role and interaction of imprinted genes in human fetal growth |
title_full | The role and interaction of imprinted genes in human fetal growth |
title_fullStr | The role and interaction of imprinted genes in human fetal growth |
title_full_unstemmed | The role and interaction of imprinted genes in human fetal growth |
title_short | The role and interaction of imprinted genes in human fetal growth |
title_sort | role and interaction of imprinted genes in human fetal growth |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4305174/ https://www.ncbi.nlm.nih.gov/pubmed/25602077 http://dx.doi.org/10.1098/rstb.2014.0074 |
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