Blood-derived gene-expression profiling in unravelling susceptibility to recessive disease.
Identification of new disease predisposition genes with chip-based technologies typically requires extensive financial and sample resources. We have recently shown that combining peripheral blood genome and transcriptome (BGT) information in highly selected materials can be a successful low-cost approach to unravelling dominant tumour susceptibility. In this study, we extended our investigations to recessively inherited tumour predisposition, and identified a homozygous germline mutation in the damage-specific DNA binding protein 2 (DDB2) gene in a patient with several facial tumours, for which doctors had been unable to provide a diagnosis. Our results provide proof of principle that BGT is a powerful approach for both dominant and recessive genes. In addition to tumour susceptibility, the method may be useful in characterising genetic defects underlying other disease phenotypes.
Department of Medical Genetics, University of Helsinki, Helsinki, Finland.
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Vahteristo
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Kokko
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Saksela
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Aittomäki
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Aaltonen
D002278:Carcinoma in Situ / Q000235:genetics; D002280:Basal Cell Carcinoma / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002648:Child; D055313:Cystatin B; D015891:Cystatins / Q000235:genetics; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D004831:Epilepsies, Myoclonic / Q000235:genetics; D005153:Facial Neoplasms / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods*; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009378:Neoplasms, Multiple Primary / Q000235:genetics*; D009669:Nose Neoplasms / Q000235:genetics*; D012313:RNA / Q000097:blood* / Q000235:genetics; D014466:Ultraviolet Rays / Q000009:adverse effects; D014983:Xeroderma Pigmentosum / Q000145:classification / Q000235:genetics*
C524994:CSTB protein, human; D015891:Cystatins; C117669:DDB2 protein, human; D004268:DNA-Binding Proteins; D012313:RNA; D055313:Cystatin B