The present invention provides methods for reducing the complexity of a nucleic acid sample to interrogate a collection of target sequences. Complexity reduction can be accomplished by annealing one or more target-specific primers to a nucleic acid sample containing genomic DNA and elongating the primers using a DNA polymerase with a high processivity rate. Labeled nucleotides or a labeled primer may be incorporated into the extension products and the labeled extension products may be separated from the unlabeled nucleic acid by affinity purification. The enriched sample may be further amplified using a target specific or non-specific amplification method. The invention further provides for analysis of the above sample to interrogate sequences of interest such as polymorphisms and to detect translocations and map translocation breakpoints. The amplified sample may be hybridized to an array, which may be specifically designed to interrogate the amplified fragments.
