Abstract for presentation at 11th International Congress of Human Genetics

Transcriptional Profiling of Maternal Uniparental Disomy 7 cell lines

  • Dr Cecilia Lindgren, Clinical Research Centre, Karolinska University Hospital, Dep. of Biosciences, Karolinska Institutet, Sweden
  • Sara Bruce, Dep. of Biosciences, Karolinska Institutet, Sweden
  • Dr Kazuhiko Nakabayashi, Dep. of Genetics and Genomic Biology, Hospital for Sick Children, Canada
  • Prof Stephen Scherer, Dep. of Genetics and Genomic Biology, Hospital for Sick Children, Canada
  • Prof Marita Lipsanen-Nyman, 4Hospital for Children and Adolescents, Helsinki University Hospital, Finland
  • Dr Katariina Hannula-Jouppi, Dep. of Medical Genetics, University of Helsinki, Finland
  • Prof Juha Kere, Clinical Research Centre, Karolinska University Hospital,Dep. of Biosciences, Karolinska Institutet, Sweden

    • Silver-Russell syndrome (SRS) occurs in children who are diagnosed with characteristic, triangular faces, low birth weight, and persistent growth retardation. Maternal uniparental disomy of chromosome 7 (matUPD7) is found in ~10% of SRS patients, whereas paternal uniparental disomy for chromosome 7 (patUPD7) shows no evidence of a SRS phenotype, suggesting that imprinting on chromosome 7 could influence the disease. So far no genes have been shown to explain how matUPD7 contributes to SRS. Thus, we set out to search for genes that would be differentially expressed between individuals with matUPD7, patUPD7, and controls.
    We established lymphoblastoid cell lines from 3 matUPD7, 2 patUPD7 patients as well as 3 control individuals. We used microarray technology (Affymetrix HGU133 plus 2.0) for global transcriptional profiling of mRNA from these cell lines.
    A moderated T-statistics was used followed by a false-discovery rate adjustment to correct for the vast number of tests. In all, one probe set turned up to show significant (corrected p=0.02) differential expression between matUPD7 as compared to patUPD7 and healthy controls. Thorough inspection of the gene showed a consistent pattern in all 5 probe sets present on the chip, with constantly lower expression levels in the matUPD7 patients. This gene, located on 17q, is currently being screened for mutations in a larger sample of SRS patients, investigating the hypothesis of whether it is involved in a SRS-pathway and possibly distorted by matUPD7. In addition we detected other genes with a similar but not statistically significant trend. These are additional candidates for growth-regulating genes.

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