Abstract
As shown by genome-wide association studies single-nucleotide polymorphisms (SNPs) within intron 1 of the FTO gene are associated with the body mass index and type II diabetes, although the functional significance of these SNPs has remained unclear. Using primer extension assays, we have determined the ratio of allelic FTO transcript levels in unspliced heterogeneous nuclear RNA preparations from blood of individuals heterozygous for SNP rs9939609. Allelic expression ratios of the neighboring RPGRIP1L gene were investigated in individuals who were heterozygous for SNP rs4784319 and heterozygous or homozygous for rs9939609. In each of five individuals, the FTO transcripts containing the A (risk) allele of rs9939609 were more abundant than those with T allele (mean 1.38; 95% confidence interval 1.31–1.44). Similar results were obtained in a fibroblast sample. We also observed skewed allelic expression of the RPGRIP1L gene in blood, but skewing was independent of the FTO genotype. Our data suggest that increased expression of FTO is associated with increased body mass.
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Acknowledgements
We thank all individuals for donating blood and skin biopsies, physicians for drawing blood, Regina Kubica for technical assistance with fibroblast cultures and the Bundesministerium für Bildung und Forschung (NGFN plus 01GS0820) for financial support.
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The URLs used for this study are as follows: UCSC Human Genome Browser Gateway at http://genome.ucsc.edu/NCBI Single Nucleotide Polymorphism at http://www.ncbi.nlm.nih.gov/projects/SNP/HapMap Genome Browser at http://hapmap.ncbi.nlm.nih.gov/cgi-perl/gbrowse/hapmap3r2_B36/.
Supplementary Information accompanies the paper on European Journal of Human Genetics website
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Berulava, T., Horsthemke, B. The obesity-associated SNPs in intron 1 of the FTO gene affect primary transcript levels. Eur J Hum Genet 18, 1054–1056 (2010). https://doi.org/10.1038/ejhg.2010.71
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DOI: https://doi.org/10.1038/ejhg.2010.71
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