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Phenylketonuria screening registry as a resource for population genetic studies
  1. U Hannelius1,
  2. C M Lindgren2,
  3. E Melén3,
  4. A Malmberg4,
  5. U von Dobeln4,
  6. J Kere1
  1. 1Department of Biosciences at Novum, Karolinska Institutet, Stockholm
  2. 2Clinical Research Centre, Karolinska University Hospital, Stockholm Sweden
  3. 3Institute of Environmental Medicine, Karolinska Institutet
  4. 4Centre for Inherited Metabolic Diseases, Karolinska University Hospital
  1. Correspondence to:
 Ulf Hannelius
 Karolinska Institutet, Department of Biosciences, Hälsovägen 7-9, 14157 Huddinge, Sweden;


Background: Neonatal screening for metabolic diseases, involving samples stored on filter paper (Guthrie spots), provides a potential resource for genetic epidemiological studies.

Objective: To develop a method to make these dried blood spots available for large scale genetic epidemiology.

Methods: DNA from untraceable Guthrie spots was extracted using a saponin and chelex-100 based method and preamplified by improved primer preamplification. Analyses were done on 38 samples each of fresh, 10, and 25 year old Guthrie spots and the success rate determined for PCR amplification for five amplicon lengths.

Results: The method was applicable even on 25 year old samples. The success rate was 100% for 100 bp amplicons and 80% for 396 bp amplicons. Ninety four Guthrie samples were genotyped, including carriers of two different PKU mutations; all carriers were found (six R158Q, four R252W), with no false positives. Finally, 2132 anonymous samples from the Swedish PKU registry were extracted and preamplified and the allele frequencies of APOε4, PPARγ Pro12Ala, and the CCR5 32 bp deletion determined. Local variations in allele frequencies suggested subpopulation structuring. There was a significant difference (p<0.01) in regional allele frequencies for the CCR5 32 bp deletion in the Swedish population.

Conclusion: Whole genome amplification makes it feasible to conduct large genetic epidemiological studies using PKU screening registries.

  • I-PEP-L, improved primer preamplification
  • NCBI, National Center for Biotechnology Information
  • SNP, single nucleotide polymorphism
  • WGA, whole genome amplified
  • complex disease
  • population screening
  • population stratification
  • whole genome amplification

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  • Competing interests: none declared