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Extensive parent-of-origin genetic effects on fetal growth

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Background

Epigenetic effects have recently been recognized as playing a very significant role in several normal and pathological phenotypes. Imprinting, the silencing of either the paternally or maternally inherited allele, is one of the most pervasive and consistent epigenetic mechanisms across species and individuals. The majority of imprinted loci are involved in fetal growth regulation, and several defects in the epigenetic regulation of these genes are associated with extremes of fetal growth.

Materials and methods

We surveyed 62 SNPs across 17 genes (Table 1) in a cohort of African-American mother-newborn pairs selected using stringent inclusion/exclusion criteria intended to enrich for the genetic component of fetal growth regulation. All association analyses were adjusted for admixture using a suite of ancestry informative SNP markers. By inferring haplotypes within the imprinted loci in mothers and newborns, we could unambiguously infer the parental origin of haplotypes and associated alleles in the majority of newborns.

Table 1 SNPs Genotyped

Results and conclusion

We found very significant parent-of-origin effects in the insulin, H19 and GNAS genes that were completely consistent with their known patterns of imprinting. In the case of the insulin polymorphisms, a consistent trend was also observed for newborn IGF-II levels with respect to parental origin of haplotypes.

Acknowledgements

This work was supported by grants to RMA from the National Institute of Child Health and Human Development (HD055462), the Children's Foundation Research Center of Memphis, the University of Tennessee Health Science Center's Clinical Translational Science Institute, and the Accredo Foundation. Support was also provided to GS from The Urban Child Institute to support the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) study.

Author information

Correspondence to Ronald M Adkins.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Cite this article

Adkins, R.M., Krushkal, J., Somes, G. et al. Extensive parent-of-origin genetic effects on fetal growth. BMC Bioinformatics 10, A13 (2009). https://doi.org/10.1186/1471-2105-10-S7-A13

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Keywords

  • Significant Role
  • Genetic Effect
  • Association Analysis
  • Fetal Growth
  • Genetic Component