Combinatorial sequencing-by-hybridization: analysis of the NF1 gene

Neurofibromatosis type 1 (NF1), one of the most common autosomal dominant disorders, is caused by mutations in the NF1 gene. A variety of methods are currently used in clinical settings to define disease-causing mutations. We describe microarray-based combinatorial sequencing-by-hybridization (cSBH), which overcomes some disadvantages associated with other techniques. Sequence readout of 2 kb was achieved on a single slide, with detection of base substitutions, insertions and small deletions. In addition, cSBH analysis of the entire NF1 gene demonstrates reproducibility, efficiency and reduced time; therefore, representing an alternative to extensive DNA sequence characterization.