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.
Vahteristo
P
P
Department of Medical Genetics, University of Helsinki, Helsinki, Finland.
Kokko
A
A
Saksela
O
O
Aittomäki
K
K
Aaltonen
L A
LA
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