The present invention provides methods for isolation of a member of a population which has one or more mutation(s) in one or more target sequence(s) in a population. The method may comprise the steps of: (a) pooling genomic DNA isolated from each member of the population in one or more dimensions (b) amplifying the one or more target sequence(s) in the pooled genomic DNA, wherein optionally the amplification products are pooled (c) sequencing the amplified products or obtaining the sequence reads for the amplified products, wherein, optionally, sequencing is by pair-end sequencing and further comprises merging the paired-end reads into composite read(s) (d) identifying the mutation(s) based on alignment-free sequence analysis of sequencing data, optionally by k-mer analysis and (e) identifying individual member(s) of the population comprising the one or more identified mutations in the target sequences, optionally by high-resolution DNA melting (HRM).
