Human Genetics

, Volume 122, Issue 6, pp 625–634 | Cite as

A genome-wide approach to identifying novel-imprinted genes

  • Katherine S. PollardEmail author
  • David Serre
  • Xu Wang
  • Heng Tao
  • Elin Grundberg
  • Thomas J. Hudson
  • Andrew G. Clark
  • Kelly Frazer
Original Investigation


Genomic imprinting is an epigenetic process in which the copy of a gene inherited from one parent (maternal or paternal) is consistently silenced or expressed at a significantly lower level than the copy from the other parent. In an effort to begin a systematic genome-wide screen for imprinted genes, we assayed differential allelic expression (DAE) at 3,877 bi-allelic protein-coding sites located in 2,625 human genes in 67 unrelated individuals using genotyping microarrays. We used the presence of both over- and under-expression of the reference allele compared to the alternate allele to identify candidate-imprinted genes. We found 61 genes with at least twofold DAE plus “flipping” of the more highly expressed allele between reference and alternate across heterozygous samples. Sixteen flipping genes were genotyped and assayed for DAE in an independent data set of lymphoblastoid cell lines from two CEPH pedigrees. We confirmed that PEG10 is paternally expressed, identified one gene (ZNF331) with multiple lines of data indicating it is imprinted, and predicted several additional imprinting candidate genes. Our findings suggest that there are at most several hundred genes in the human genome that are universally imprinted. With samples of mRNA from appropriate tissues and a collection of informative cSNPs, a genome-wide search using this methodology could expand the list of genes that undergo genomic imprinting in a tissue- or temporal-specific manner.


Imprint Gene CEPH Heterozygous Individual Pedigree Analysis Reference Allele 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



At Perlegen Sciences we thank Erica J. Beilharz for project management assistance, Geoff B. Nilsen for designing the high-density array, and P.V. Pant for assistance with data analysis. At McGill University we thank Scott Gurd for technical assistance, Tomi M. Pastinen for supporting the osteoblast work and helpful discussions, and Olof Nilsson at Uppsala University, Sweden for collecting the bone samples for the osteoblast panel. T.J. Hudson is the recipient of a Clinician-Scientist Award in Translational Research by the Burroughs Wellcome Fund. This work was supported by an NHGRI grant to K.A. Frazer and by Genome Canada and Genome Quebec grants to T.J. Hudson. K.A. Frazer is a former employee of Perlegen Sciences, Inc.

Supplementary material

439_2007_440_MOESM1_ESM.doc (1008 kb)
Supplementary Figures (DOC 0.98 MB)
439_2007_440_MOESM2_ESM.xls (217 kb)
Supplementary Tables (XLS 217 kb)


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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Katherine S. Pollard
    • 1
    Email author
  • David Serre
    • 2
  • Xu Wang
    • 3
  • Heng Tao
    • 5
  • Elin Grundberg
    • 2
  • Thomas J. Hudson
    • 2
    • 4
  • Andrew G. Clark
    • 3
  • Kelly Frazer
    • 5
    • 6
  1. 1.UC Davis Genome Center and Department of StatisticsUniversity of CaliforniaDavisUSA
  2. 2.McGill University and Genome Quebec Innovation CentreMontrealCanada
  3. 3.Department of Molecular Biology and GeneticsCornell UniversityIthacaUSA
  4. 4.Ontario Institute for Cancer ResearchTorontoCanada
  5. 5.Perlegen SciencesMountain ViewUSA
  6. 6.Scripps Genomic MedicineLa JollaUSA

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