Abstract: Flexible and scale methods of genotyping-by sequencing are provided. Typically the methods include the steps of cutting genomic DNA into blunt-ended fragments using a blunt-cutting restriction endonuclease enzyme, dA tailing the fragments and ligating the dA tailed fragments to universal sequencing adapters, enrichment of desired DNA by size-selecting, barcoding and sequencing the size-selected fragments of the genomic DNA. A standard DNA size selection step can be used to capture a small portion of the genome that will be consistent between samples from the same species. The methods improve the efficiency, coverage, data quality and cost over existing methods for reduced representation sequences of genomes.