Double Digest Restriction Associated DNA (ddRAD) Sequencing. Is a protocol that builds on the RADseq which differs in two principal respects: First, eliminates random shearing and end repair of genomic DNA (an advantage shared with a family of partially overlapping protocols such as MSG, CrOPS, and other recent RADseq derivatives.  Instead, it  use a double restriction enzyme (RE) digest resulting in at least five-fold reduction in library production cost–complete ddRADseq libraries cost ∼$5 per sample.  Furthermore, the elimination of several high-DNA-loss steps permits construction of ddRAD libraries from 100 ng or less of starting DNA. Second, introduced a precise selection for genomic fragments by size, which allows greater fine-scale control of the fraction of regions represented in the final library. By combining precise and repeatable size selection with sequence-specific fragmentation, double digest Restriction-Site Associated DNA sequencing (ddRADseq) produces sequencing libraries consisting of only the subset of genomic restriction digest fragments generated by cuts with both Res and which fall within the size-selection window. This combination of requirements can be tuned to generate libraries consisting of fragments derived from hundreds to hundreds of thousands of regions genome-wide. ( Source From Brant K. Peterson, Jesse N. Weber, Emily H. Kay, Heidi S. Fisher, Hopi E. Hoekstr. Double Digest RADseq: An Inexpensive Method for De Novo SNP Discovery and Genotyping in Model and Non-Model Species. PLoS ONE. May 2012 ; 7; 5) :e37135)