ERP005535 PRJEB6072 ena-STUDY-HUBRECHT INSTITUTE, UTRECHT, THE NETHERLANDS-08-04-2014-16:21:59:670-222 Resequencing of selected loci from chromosome conformation capture templates Gene function can be affected by many types of genetic changes including single nucleotide variants, small indels and structural variants. Robust detection of all relevant variation in and around genes of interest remains a challenge despite rapid developments in targeted and whole genome DNA analysis techniques1. Here we present a conceptually novel strategy called Targeted Locus Amplification (TLA) that enables complete sequencing of selected genes. TLA uses spatial proximity to selectively enrich the chromosomal parts that neighbor a selected sequence in a locus of interest, for analysis by next generation sequencing. We show that TLA has a range of additional applications, uncovering viral and transgene integration sites and identifying chromosomal rearrangement partners at basepair resolution. Structural variants and gene fusions in the clinically relevant BRCA genes could be identified that went previously unnoticed. Finally, we show that TLA enables haplotyping across large chromosomal intervals. TLA can therefore give complete sequence information of any gene of interest. Targeted Locus Amplication Gene function can be affected by many types of genetic changes including single nucleotide variants, small indels and structural variants. Robust detection of all relevant variation in and around genes of interest remains a challenge despite rapid developments in targeted and whole genome DNA analysis techniques1. Here we present a conceptually novel strategy called Targeted Locus Amplification (TLA) that enables complete sequencing of selected genes. TLA uses spatial proximity to selectively enrich the chromosomal parts that neighbor a selected sequence in a locus of interest, for analysis by next generation sequencing. We show that TLA has a range of additional applications, uncovering viral and transgene integration sites and identifying chromosomal rearrangement partners at basepair resolution. Structural variants and gene fusions in the clinically relevant BRCA genes could be identified that went previously unnoticed. Finally, we show that TLA enables haplotyping across large chromosomal intervals. TLA can therefore give complete sequence information of any gene of interest.