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Genetic variations and normal fetal growth.

D B Dunger1, C J Petry, K K Ong

  • 1Department of Paediatrics, University of Cambridge, Addenbrooke's Hospital, UK. dbd25@cam.ac.uk

Hormone Research
|April 14, 2006
PubMed
Summary

Fetal growth is influenced by genetics, but the maternal environment, especially in first pregnancies, restrains growth. Paternally expressed genes may significantly impact fetal size when maternal restraint is minimal.

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Area of Science:

  • Genetics
  • Developmental Biology
  • Maternal-Fetal Medicine

Background:

  • Birth size is a heritable trait, with genetics contributing 30-70% to variability.
  • Maternal environment, particularly in first pregnancies, restrains fetal growth, with this effect potentially inherited maternally.
  • Candidate genes like mitochondrial DNA 16189 and maternally expressed H19, along with insulin-like growth factors (IGF-I, IGF-II) and their receptors, are implicated in fetal growth.

Purpose of the Study:

  • To explore the genetic underpinnings of birth size, considering both maternal and fetal genetic contributions.
  • To investigate the role of common genetic variants in genes regulating fetal growth, including insulin and IGF pathways.
  • To understand how maternal restraint influences the impact of fetal genes on birth size.

Main Methods:

  • Review of existing family studies and genetic association data.
  • Examination of mouse knockout models and rare human genetic variants.
  • Analysis of common variants in genes such as H19 and INS (insulin gene).

Main Results:

  • Maternal environment restrains fetal growth, most notably in first pregnancies.
  • Common variation in the insulin gene (INS) variable number tandem repeats is linked to birth size, particularly in later pregnancies with less maternal restraint.
  • Paternally expressed genes may play a significant role in fetal growth when maternal restraint is reduced.

Conclusions:

  • While maternal factors influence fetal growth, fetal genes, especially paternally expressed ones, appear to significantly affect birth size in specific pregnancy contexts.
  • Further research is needed to clarify the complex interplay between maternal environment and fetal genetics in determining birth weight.
  • Investigating common genetic variations in key growth regulatory genes is crucial for a comprehensive understanding of birth size determination.

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