Volume 10 Supplement 7

UT-ORNL-KBRIN Bioinformatics Summit 2009

Open Access

Extensive parent-of-origin genetic effects on fetal growth

  • Ronald M Adkins1Email author,
  • Julia Krushkal2,
  • Grant Somes2,
  • John Fain3,
  • John Morrison4,
  • Chad Klauser4 and
  • Everett F Magann5
BMC Bioinformatics200910(Suppl 7):A13

DOI: 10.1186/1471-2105-10-S7-A13

Published: 25 June 2009

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

INSIG2

rs7566605

GRB10

rs2074778

H19

rs2839703

GNAS

rs965808

IGFBP2

rs9341090

 

rs2282931

 

rs217727

 

rs1800902

 

rs3770473

 

rs6945597

 

rs2067051

 

rs6123832

 

rs9341178

 

rs7791286

 

rs2251375

 

rs6026576

GHRL

rs35684

LEP

rs10249476

 

rs4929984

 

rs6092704

 

rs4684677

 

rs12535708

IGF2

rs680

 

rs2057291

 

rs696217

 

rs7799039

 

rs3213233

 

rs7121

 

rs26802

 

rs2167270

 

rs734351

 

rs234621

GHSR

rs509035

 

rs10954173

IGF2AS

rs1003483

Ancestry

rs2814778

 

rs572169

 

rs3828942

 

rs3741206

Informative

rs11903376

 

rs512692

CPA4

rs6942830

 

rs3741205

 

rs17614025

ADIPO

rs266729

 

rs1038627

 

rs3741204

 

rs7732591

 

rs182052

 

rs3800775

 

rs1004446

 

rs9321552

EDN1

rs2070698

MEST

rs1005171

INS

rs3842756

 

rs1426492

 

rs2070699

GAD2

rs2839670

 

rs3842748

 

rs12677824

 

rs5369

 

rs2236418

 

rs689

 

rs803733

 

rs5370

TCF7L2

rs7903146

 

rs3842738

 

rs161272

ENPP1

rs1044498

 

rs10885406

   

rs680273

 

rs7754561

     

rs3825663

       

rs735480

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.

Declarations

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.

Authors’ Affiliations

(1)
Department of Pediatrics, University of Tennessee Health Science Center
(2)
Department of Preventive Medicine, University of Tennessee Health Science Center
(3)
Department of Molecular Sciences, University of Tennessee Health Science Center
(4)
Department of Obstetrics and Gynecology, University of Mississippi Medical Center
(5)
Department of Obstetrics and Gynecology, Naval Medical Center at Portsmouth

Copyright

© Adkins et al; licensee BioMed Central Ltd. 2009

This article is published under license to BioMed Central Ltd.

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