de Vree, P.J.P. et al. Nat. Biotechnol. 10.1038/nbt.2959 (17 August 2014).
Targeted resequencing methods are widely used, but these techniques do not discriminate between alleles and typically require that much of the target sequence be known. de Vree et al. exploit the observation that proximity ligation–based assays such as chromosome conformation capture on-chip (4C) are highly enriched for neighboring DNA sequences. Their new targeted locus amplification (TLA) method begins with a single anchor sequence and, unlike 4C, does not enrich for contact points after a second digestion step. Mainly using the BRCA genes, the authors demonstrate TLA for resequencing tens to hundreds of kilobases, haplotyping, assessing genetic and structural variation, and sequencing transgene integration sites.
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Sampling local sequence with proximity ligation. Nat Methods 11, 991 (2014). https://doi.org/10.1038/nmeth.3123
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DOI: https://doi.org/10.1038/nmeth.3123